TargetingAutophagyinCancerJeanM.MulcahyLevy1,2,3,ChristinaG.Towers3,andAndrewThorburn3,41DepartmentofPediatrics,UniversityofColoradoSchoolofMedicine,Aurora,CO80045,USA2MorganAdamsFoundationPediatricBrainTumorResearchProgram,Children’sHospitalColorado,Aurora,UnitedStates3DepartmentofPharmacology,UniversityofColoradoSchoolofMedicine,Aurora,CO80045,USA4DepartmentofMedicine,UniversityofColoradoSchoolofMedicine,Aurora,CO80045,USAPrefaceAutophagyisamechanismbywhichcellularmaterialisdeliveredtolysosomesfordegradationallowingbasalturnoverofcellcomponentsandprovidingenergyandmacromolecularprecursors.Autophagyhasopposing,context-dependentrolesincancerandinterventionstobothstimulateandinhibitautophagyhavebeenproposedascancertherapies.Thishascausedtherapeutictargetingofautophagyincancertobesometimesviewedascontroversial.Herewesuggestawayforwardforeffectivetargetingofautophagybyunderstandingthecontext-dependentrolesofautophagyandcapitalizingonmodernapproachestoclinicaltrialdesign.IntroductionAdvancementsintheunderstandingofautophagyandhowwecanharnessthispathwaytoimproveclinicaloutcomeshavecomealongwaysincetheintroductionofthetermbyChristiandeDuvein19631(Fig1).TheimportanceofautophagyinhealthanddiseasewasrecentlyhighlightedwhenYoshinoriOhsumiwasawardedtheNobelPrizeforPhysiologyorMedicineforhisworkelucidatingthemechanismofautophagy2.Ofparticularimportanceistheroleofautophagyincancer.Itisthoughtthatautophagypreventscancerdevelopment.Conversely,oncecancerisestablished,increasedautophagicfluxoftenenablestumorcellsurvivalandgrowth3,4.Thusanimportantquestionforcancertherapyisshouldwetrytoenhanceautophagyorinhibitit?Inpremalignantlesionsmuchevidencesuggeststhatenhancersofautophagymightpreventcancerdevelopment5.Conversely,inadvancedCorrespondence:Andrew.Thorburn@ucdenver.edu.CompetingInterestsStatementTheauthorsdeclarenocompetinginterests.SubjectCategoriesBiologicalsciences/Cellbiology/Autophagy[URI/631/80/39];Biologicalsciences/Cellbiology/Celldeath[URI/631/80/82]Biologicalsciences/...
