SeminarsinCancerBiology44(2017)25–42ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewThechallengeoftargetingcancerstemcellstohaltmetastasisAliceAglianoa,∗,AlfonsoCalvob,CarolBoxaaCancerResearchUKCancerImagingCentre,DivisionofRadiotherapyandImaging,TheInstituteofCancerResearchandTheRoyalMarsdenNHSFoundationTrust,123OldBromptonRoad,London,SW73RP,UnitedKingdombCIBERONC/IDISNAProgramofSolidTumoursandBiomarkers,CIMAoftheUniversityofNavarraandDepartmentofHistologyandPathology,SchoolofMedicine,UniversityofNavarra,Pamplona,SpainarticleinfoArticlehistory:Received30December2016Receivedinrevisedform10March2017Accepted13March2017Availableonline18March2017Keywords:CancerstemcellEpithelial-to-mesenchymaltransitionMetastasisMicroenvironmentTherapyresistanceabstractDespiteacontinuingdebateabouttheexistenceofcancerstemcells(CSCs),recentdiscoverieshaveprovidedfurthersupportfortheirexistenceandtheirrolesindrugresistance,cancerrecurrenceandmetastasis.CSCcharacteristics,suchasself-renewalandtumourinitiation,andsupportingcellularpro-cesses,particularlytheepithelial-to-mesenchymaltransition,areattractingagreatdealofattentionfromcancerresearchersastheyofferopportunitiesfordiscoveringnoveltherapeutictargetsforfuturedrugdevelopment.However,theidentificationofpotentialCSCtargetspresentsclearobstaclesduetoalackoftrulyspecificCSCmarkersandtherealityofCSCplasticity,makingthistaskasignificantchallenge.Agentsthattargetdevelopmentalsignallingpathways,suchasNotch,WntandHedgehog,arenowinclinicaltrialswhilstalternativeapproachesincludingimmune-basedtherapiesandmicroRNA-mediatedpathwayinhibitorsareproducingpromisingpre-clinicalresults.Here,wediscussthecontributionofCSCstocancermetastasisandthescopeofopportunitiesfortherapeuticintervention.Inparticular,weconsiderCSC-targetingagentsforwhichthereisexperimentalevidenceofanti-metastaticpropertiesandwhichmayhavepotentialtoeventuallylimitrelapseandimpedemetastasisinpatients.©2017TheAuthor...
