ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewPancreaticcancerstemcells:Astateoranentity?PatrickC.Hermanna,BrunoSainzJr.b,c,d,⁎aDepartmentofInternalMedicineI,UlmUniversity,GermanybDepartmentofBiochemistry,UniversidadAutónomadeMadrid(UAM),Madrid,SpaincDepartmentofCancerBiology,InstitutodeInvestigacionesBiomédicas“AlbertoSols”(IIBM),CSIC-UAM,Madrid,SpaindChronicDiseasesandCancer,Area3-InstitutoRamónyCajaldeInvestigaciónSanitaria(IRYCIS),Madrid,SpainARTICLEINFOKeywords:PancreaticductaladenocarcinomaCancerstemcellsPlasticityTumormicroenvironmentCancerstemcellnicheCancerstemcelltargetedtherapiesABSTRACTPancreaticductaladenocarcinoma(PDAC),themostcommontypeofpancreaticcancer,hasamedianoverallsurvivalof6–12monthsanda5-yearsurvivaloflessthan7%.WhilePDACcurrentlyrepresentsthe4thmostfrequentcauseofdeathduetocancerworldwide,itisexpectedtobecomethesecondleadingcauseofcancer-relateddeathby2030.Thesealarmingstatisticsareprimarilyduetoboththeinherentchemoresistantandmetastaticnatureofthistumor,andtheexistenceofasubpopulationofhighlyplastic“stem”-likecellswithinthetumor,knownascancerstemcells(CSCs).SincetheirdiscoveryinPDACin2007,wehavecometorealizethatpancreaticCSCshaveuniquemetabolic,autophagic,invasive,andchemoresistancepropertiesthatallowthemtocontinuouslyself-renewandescapechemo-therapeuticelimination.Moreimportantly,theconceptoftheCSCasafixedentitywithinthetumorhasalsoevolved,andcurrentdatasuggestthatCSCsarestatesratherthandefinedentities.Consequently,currenttreatmentsforthemajorityofPDACpatientsarenoteffective,anddonotsignificantlyimpactoverallpatientsurvival,astheydonotadequatelytargettheplasticCSCsub-populationnorthetransient/hybridcellsthatcanreplenishtheCSCpool.Thus,itisnecessarythatweimproveourunder-standingofthecharacteristicsandsignalsthatmaintainanddrivethepancreaticCSCpopulationinordertodevelopnewtherapiestotargetthesecells.Herein,wewillprovidethelatestupdatesandknowledgeontheinherentc...
