ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewApromisingnewapproachtocancertherapy:TargetingironmetabolismincancerstemcellsMouradiElHouta,b,LeïlaDosSantosa,b,AhmedHamaïa,b,⁎,MaryamMehrpoura,b,⁎aInstitutNecker-EnfantsMalades(INEM),InsermU1151-CNRSUMR8253,FrancebUniversitéParisDescartes-SorbonneParisCité,F-75993Paris,FranceARTICLEINFOKeywords:CancerstemcellsIronmetabolismFerroptosisCancertherapyCellsignalingEpigeneticABSTRACTIronisanessentialnutrientthatfacilitatescellproliferationandgrowth.Ironcanbedetrimental,however.Theabilityofirontocyclebetweenoxidizedandreducedformscontributestotheformationoffreeradicals.Anexcessoffreeradicalsleadstolipidperoxidation,morereactiveoxygenspeciesandoxidativestress,damagetoDNAandotherbiomolecules,and,ifpotentially,tumorigenesis.Ironalsohasaroleinthemaintenanceofthetumormicroenvironmentandinmetastasis.Pathwaysofironacquisition,efflux,storage,andregulationareallperturbedincancer,suggestingthatreprogrammingofironmetabolismisacentralaspectoftumorcellsurvival.Recentstudieshaveshedlightontheroleofironmetabolismincancerstemcells(CSC)andsuggestthatspecifictargetingofironmetabolisminCSCsmayimprovetheefficacyofcancertherapy.Inthisreview,wefirstsummarizebrieflyourcurrentunderstandingoftheintracellularprocessesinvolvingiron,theeffectofdietaryiron,anditsrelationtocancer.Weemphasizetheimportanceofmodifier“irongenes”incancerandthepos-sibilitythatthesegenesmayencodebiomarkersthatmaybeusedclinically.Wethenprovideanupdateontheroleofironinmetabolicreprogramming,theepithelial-mesenchymaltransition,andtheregulationofepigeneticmarksessentialforCSCmaintenanceandplasticity.Finally,wediscussthepotentialoftargetingarecentlydiscoveredformofiron-regulatedcelldeath,ferroptosis,inCSCsfortreatmentofcancer.1.IntroductionIronisanutrientessentialforhemoglobinsynthesis,DNAsynthesis,andenergymetabolisminallmammals.Ironisalsoanessentialcom-ponentofvariousproteinsinvolvedinmitochondrialrespir...
