1904197(1of25)©2019WILEY-VCHVerlagGmbH&Co.KGaA,Weinheimwww.advmat.deProgressrePortRecentProgressinFerroptosisInducersforCancerTherapyChenLiang,XinglinZhang,MengsuYang,*andXiaochenDong*DOI:10.1002/adma.201904197celldeath”(RCD).[2]UnderstandinghowtheRCDprocessesaremodulatedbyinternalandexternalfactorsisofgreattherapeuticinterest.[3,4]Historically,celldeathwasclassifiedintothreecategoriesbasedontheirmor-photypes:1)typeI,apoptosis;2)typeII,autophagy;and3)typeIII,necrosis.[1]Amongwhichthecaspase-dependentapoptosishaslongbeenconsideredastheonlyformofRCDandisadoptedforthedevelopmentofanticancerdrugs.[5]However,thetherapeuticoutcomesofthosedrugsarefarfromsatisfactoryduetotheintrinsicoracquiredapoptosisresistanceofcancercells.Forinstance,asaself-defenseresponse,drugresistanceoccursfrequentlyincancercellsupontheinductionofapoptosisbychemothera-peutics.[6,7]Mutationshavebeenobservedinmanycancercelltypesthatcanevadeapoptosis,whichresultintreatmentfailure.[8]Insomecases,theoverexpressionofapoptosisinhibitorscanreducethera-peuticeffectivenessinmalignantcells.[9,10]Recently,ourtradi-tionalunderstandingofcelldeathprocesshasbeenchallengedbythediscoveryofseveralnovelcelldeathprocesseswithuniqueregulatorypathways.SomeofthesenewlydiscoveredRCDsthatsharedifferentmechanismswithapoptosiscancir-cumventitslimitations,whichopenupnewopportunitiestotreatcancer.[11]Amongthesenon-apoptoticformsofRCDs,ferroptosishasreceivedconsiderableattentionduetoitsinvolvementindevelopment,immunity,senescence,andavarietyofpathologicalscenarios.Ferroptosisisdefinedasanoxidative,iron-dependentformofRCDthatischaracterizedbyaccumu-lationofreactiveoxygenspecies(ROS)andlipidperoxidationproductstolethallevels.[12,13]Despitetheimportantroleofferroptosisinsustainingsurvivalofnormalcellsandtissues,ithasbeenincreasinglyrecognizedthatsomeoncogenicpath-waysarerelatedtoferroptosis,renderingcancercellsextremelyvulnerabletoferroptoticdeath.[14]Asoneofthemostwell-studiedtumorsuppressorgenes,p53inhibitstheexpressionofcysti...
