ArticleMulti-stageDifferentiationDefinesMelanomaSubtypeswithDifferentialVulnerabilitytoDrug-InducedIron-DependentOxidativeStressGraphicalAbstractHighlightsdMelanomadifferentiationinvolvesfourprogressivestepwisestatesdDifferentiationistwo-dimensionalwithanintermediateneuralcrestsignaturedMelanomadedifferentiationincreasessensitivitytoferroptosisdCo-targetingferroptosiscanblockthededifferentiationresistanceescaperouteAuthorsJenniferTsoi,LidiaRobert,KimParaiso,...,NicolaosPalaskas,AntoniRibas,ThomasG.GraeberCorrespondencetgraeber@mednet.ucla.eduInBriefTsoietal.showthatmelanomacanbecategorizedintofoursubtypesfollowingadifferentiationtrajectorywithsubtype-specificsensitivitytoferroptosisinduction,whichpresentsatherapeuticapproachtotargetthedifferentiationplasticitytoincreasetheefficacyoftargetedandimmunetherapies.Tsoietal.,2018,CancerCell33,890–904May14,2018ª2018ElsevierInc.https://doi.org/10.1016/j.ccell.2018.03.017CancerCellArticleMulti-stageDifferentiationDefinesMelanomaSubtypeswithDifferentialVulnerabilitytoDrug-InducedIron-DependentOxidativeStressJenniferTsoi,1,2LidiaRobert,3KimParaiso,1,2CarlosGalvan,1,2KatherineM.Sheu,1,2JohnsonLay,1,2,5DeborahJ.L.Wong,3MohammadAtefi,3RoksanaShirazi,1,2XiaoyanWang,4DanielBraas,1,2,5CatherineS.Grasso,3NicolaosPalaskas,1,2AntoniRibas,1,3,6,7andThomasG.Graeber1,2,5,7,8,9,*1DepartmentofMolecularandMedicalPharmacology,UniversityofCalifornia,LosAngeles(UCLA),570WestwoodPlaza,Building114,LosAngeles,CA90095,USA2CrumpInstituteforMolecularImaging,UCLA,LosAngeles,CA90095,USA3DepartmentofMedicine,UCLA,LosAngeles,CA90095,USA4DepartmentofMedicineStatisticsCore,UCLA,LosAngeles,CA90095,USA5UCLAMetabolomicsCenter,LosAngeles,CA90095,USA6DepartmentofSurgery,DivisionofSurgical-Oncology,UCLA,LosAngeles,CA90095,USA7JonssonComprehensiveCancerCenter,UCLA,LosAngeles,CA90095,USA8CaliforniaNanoSystemsInstitute,UCLA,LosAngeles,CA90095,USA9LeadContact*Correspondence:tgraeber@mednet.ucla.eduhttps://doi.org/10.1016/j.ccell.2018.03.017SUMMARYMalignanttransf...
