Pharmacologicalmodulationofautophagy:therapeuticpotentialandpersistingobstaclesLorenzoGalluzzi1,2,*,JoséManuelBravo-SanPedro2,3,4,5,6,*,BethLevine7,8,DouglasR.Green9,andGuidoKroemer2,3,4,5,6,10,111DepartmentofRadiationOncology,WeillCornellMedicalCollege,NewYork,NewYork10065,USA2UniversitéParisDescartes/ParisV,SorbonneParisCité,Paris75006,France3UniversitéPierreetMarieCurie/ParisVI,Paris75006,France4Equipe11labelliséeLiguecontreleCancer,CentredeRecherchedesCordeliers,Paris75006,France5INSERM,U1138,Paris75006,France6MetabolomicsandCellBiologyPlatforms,GustaveRoussyComprehensiveCancerInstitute,Villejuif94805,France7CenterforAutophagyResearch,UniversityofTexasSouthwesternMedicalCenter,Dallas,Texas75390,USA8HowardHughesMedicalInstitute,Dallas,Texas75390,USA9StJudeChildren’sResearchHospital,Memphis,Tennessee38105,USA10KarolinskaInstitute,DepartmentofWomen’sandChildren’sHealth,KarolinskaUniversityHospital,Stockholm17176,Sweden11PôledeBiologie,HopitâlEuropéenGeorgePompidou(AP-HP),Paris75015,FranceAbstractAutophagyiscentraltothemaintenanceoforganismalhomeostasisinbothphysiologicalandpathologicalsituations.Accordingly,alterationsinautophagyhavebeenlinkedtoclinicallyrelevantconditionsasdiverseascancer,neurodegenerationandcardiacdisorders.Throughoutthepastdecade,autophagyhasattractedconsiderableattentionasatargetforthedevelopmentofnoveltherapeutics.However,sucheffortshavenotyetgeneratedclinicallyviableinterventions.InthisReview,wediscussthetherapeuticpotentialofautophagymodulators,analysetheobstaclesthathavelimitedtheirdevelopmentandproposestrategiesthatmayunlockthefulltherapeuticpotentialofautophagymodulationintheclinic.CorrespondencetoL.G.deadoc@vodafone.it.*Theseauthorscontributedequallytothiswork.CompetinginterestsstatementTheauthorsdeclarenocompetinginterests.Publisher’snoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.HHSPublicAccessAuthormanuscriptNatRevDrugDiscov.Authormanuscript;availableinPMC2017...
