ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerTherapyresistancemediatedbycancerstemcellsTeresaBernadetteSteinbichlera,JózsefDudása,SergejSkvortsovb,c,UteGanswindtb,HerbertRiechelmanna,Ira-IdaSkvortsovab,c,⁎aDepartmentofOtorhinolaryngology,HeadandNeckSurgery,MedicalUniversityofInnsbruck,Innsbruck,AustriabDepartmentofTherapeuticRadiologyandOncology,MedicalUniversityofInnsbruck,Innsbruck,AustriacEXTRO-Lab,TyroleanCancerResearchInstitute,Innsbruck,AustriaARTICLEINFOKeywords:CancerstemcellsDormancyEMTDNArepairStemcellnicheABSTRACTCancerstemcells(CSC)possessabilitiesgenerallyassociatedwithembryonicoradultstemcells,especiallyself-renewalanddifferentiation.TheCSCmodelassumesthatthissubpopulationofcellssustainsmalignantgrowth,whichsuggestsahierarchicalorganizationoftumorsinwhichCSCsareontopandresponsibleforthegenerationofintratumoralheterogeneity.EffectivetumortherapyrequirestheeradicationofCSCastheycansupportregrowthofthetumorresultinginrecurrence.However,eradicationofCSCisdifficultbecausetheyfrequentlyaretherapyresistant.Therapyresistanceismediatedbytheacquisitionofdormancy,increasedDNArepairanddrugeffluxcapacity,decreasedapoptosisaswellastheinteractionbetweenCSCandtheirsupportingmicro-environment,theCSCniche.ThisreviewhighlightstheroleofCSCinchemo-andradiotherapyresistanceaswellaspossiblewaystoovercomeCSCmediatedtherapyresistance.1.IntroductionTumorsconsistofheterogeneouscellpopulationsincludingcancerstemcells(CSC).SinceCSCaretumorigenic,amoreappropriatetermforthemmightbe“tumorinitiatingcells”becausetheyareabletoproduceallcelltypesfoundinaparticulartumor.ThetermCSCisroutinelyusedbecausethesetumor-initiatingcellshaveabilitiesasso-ciatedwithnormalstemcells,especiallytheabilityofself-renewalanddifferentiation[1–4].CSCarenotauniformcelltype,insteadtheCSCphenotypemightbedifferentforcancersubtypesandmayevenvaryinthesamecancerovertime[5,6].Accordingly,CSCexpressspecificmarkersthatvaryconsiderablydependingont...
