CancerCellReviewTargetingFerroptosistoIronOutCancerBehrouzHassannia,1,2PeterVandenabeele,1,2,3andTomVandenBerghe1,2,4,5,*1VIBCenterforInflammationResearch(IRC),Ghent,Belgium2DepartmentofBiomedicalMolecularBiology(DBMB),GhentUniversity,Ghent,Belgium3MethusalemProgram,GhentUniversity,Ghent,Belgium4LaboratoryofPathophysiology,DepartmentofBiomedicalSciences,UniversityofAntwerp,2000Antwerp,Belgium5FerroptosisAndInflammationResearch(FAIR),VIB-GhentUniversityandUniversityofAntwerp,Belgium*Correspondence:tom.vandenberghe@uantwerp.behttps://doi.org/10.1016/j.ccell.2019.04.002Oneofthekeychallengesincancerresearchishowtoeffectivelykillcancercellswhileleavingthehealthycellsintact.Cancercellsoftenhavedefectsincelldeathexecutionermechanisms,whichisoneofthemainreasonsfortherapyresistance.Toenablegrowth,cancercellsexhibitanincreasedirondemandcomparedwithnormal,non-cancercells.Thisirondependencycanmakecancercellsmorevulnerabletoiron-catalyzednecrosis,referredtoasferroptosis.TheidentificationofFDA-approveddrugsasferroptosisinducerscreateshighexpectationsforthepotentialofferroptosistobeanewpromisingwaytokillther-apy-resistantcancers.IntroductionDespiteconsiderableadvancesintreatment,cancerremainsthesecondleadingcauseofdeathworldwide(WHO,2018).Trig-geringapoptoticcelldeathwithanti-cancerdrugsisoneoftheprincipalapproachesforkillingcancercells.However,theeffec-tivenessofapoptosisinductionintumorsislimited,duetotheacquiredorintrinsicresistanceofcancercellstoapoptosis(Hol-ohanetal.,2013;OkadaandMak,2004;Suetal.,2016).There-fore,exploitingotherformsofnon-apoptoticcelldeathopensnewtherapeuticavenuesforeliminatingcancercellsandlimitingthesurvivalofdrug-resistantclones.Twodecadesofintensivecelldeathresearchhasrevealedtheexistenceofseveralmodesofregulatednecrosis(VandenBergheetal.,2014).Twotypesofregulatednecrosis,necroptosisandferroptosis,arebeingexploredasalternativewaystoeradicateapoptosis-resistantcancercells.Agrowinglistofcompoundsandanti-cancerdrugshasbeenreportedtoinitiatenecroptosis(...
