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来源:于朦胧喜获偶像张靓颖评论追星成功难掩激动之情  作者:   发表时间:2019-10-15 10:18:35

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  “MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  “MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

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