ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewOvariancancerstemcellsmorequestionsthananswersPetronellaBeatrixOttevangerDepartmentofMedicalOncology(452),RadboudUniversityMedicalCenter,PO9101,6500HBNijmegen,TheNetherlandsARTICLEINFOKeywords:OvariancancerStemcellEpithelialmesenchymaltransformationABSTRACTEpithelialovariancancerisahighlylethaldisease,whichisusuallydiagnosedatalatestagewithextensivemetastasesintheabdominalcavity.Ovariancancereitherdevelopsfromtheovariansurfaceepithelium(OSE)orfromserousintra-epithelialcarcinoma(STIC).Primarytherapyconsistsofdebulkingsurgeryandplatinumbasedchemotherapy.Thesuccessofdebulkingsurgerydependsonsurgicalskillsbutalsoonthegenesignatureofthetumour.Debulkingsurgerycombinedwithfirstlineplatinumbasedchemotherapy,frequentlyleadstocompleteremission.However,mostovariancancersrelapse.Oncethediseasehasrelapsed,theintervalbetweensubsequenttherapiesdecreasessteadilyduetorapidprogressionandtherapyresistance.Researchontherapyresistanceofovariancancerisfrequentlydevotedtogeneticalterationsincancercells,leadingtodruginactivation,enhancedDNArepairmechanismsandintracellularpathwayderangements.Howevertheknowledgeofovariancancerstemcells(OCSC)andtheroletheyplayinthedevelopmentofcancerandtherapyresistanceissparse.InthisreviewcurrentknowledgeonthecharacteristicsofOCSCsandthemicroenvironmentalmechanismsleadingtothedevelopmentoractivationofOCSCsresultinginovariancancerisreviewed.MoreovertheroleofOCSCinbothsurgicalandsystemictherapyresistanceandtherelationwithepithelialmesenchymaltransformation(EMT)isdiscussed,asaremicro-environmentalsignalsleadingtoOCSCorEMTactivation.1.IntroductionOvariancanceristhe7thmostcommoncancerinwomenworld-wideandthethirdmostcommonfemalecancerafterbreastandcervixcancer,withanincidencerateof10–15per100,000.Itisalsothe5thmostlethalcancerinwomenworldwide[1].MortalityratesarefallinginWesterncountries,butthisismorelikelyduetofallingincidenceratesresultingfromli...
