ContentslistsavailableatScienceDirectDrugResistanceUpdatesjournalhomepage:www.elsevier.com/locate/drupExosomesandtheirroleintumorigenesisandanticancerdrugresistanceNetaMilman,LanaGinini,ZivGil⁎TheLaboratoryforAppliedCancerResearch,DepartmentofOtolaryngologyHeadandNeckSurgery,TheClinicalResearchInstituteatRambamHealthcareCampus,TechnionIntegratedCancerCenter,RappaportInstituteofMedicineandResearch,Technion,IsraelInstituteofTechnology,Haifa,IsraelARTICLEINFOKeywords:ExosomesDrugresistanceTumormicroenvironmentDrugdeliveryABSTRACTExosomesareaclassofextracellularvesiclesranginginsizefrom40to100nm,whicharesecretedbybothcancercellsandmultiplestromalcellsinthetumormicroenvironment.Followingtheirsecretion,exosomespartakeinendocrine,paracrineandautocrinesignaling.Internalizationofexosomesbytumorcellsinfluencesseveralcellularpathwayswhichaltercancercellphysiology.Tumor-derivedexosomessecretedbycancerorstromalcellscanalsoconferanticancerdrug-resistanttraitsuponcancercells.Theseexosomespromoteche-moresistancebytransferringtheircargowhichincludesnucleicacids,proteins,andmetabolitestocancercellsoractasadecoyforimmunotherapeutictargets.Depletionofexosomescanreversesomeofthedetrimentaleffectsontumormetabolismandrestoredrugsensitivitytochemotherapeutictreatment.Hereinwediscussvariousapproachesthathavebeendevelopedtodepleteexosomesfortherapeuticpurposes.Thenaturalcomposition,lowimmunogenicityandcytotoxicityofexosomes,alongwiththeirabilitytospecificallytargettumorcells,renderthemanappealingplatformfordrugdelivery.Theabilityofexosomestomediateautocrineandparacrinesignalingintargetcells,alongwiththeirnaturalstructureandlowimmunogenicityrenderthemanattractivevehicleforthedeliveryofanticancerdrugstotumors.1.IntroductionExosomesareaheterogeneousclassofextracellularvesiclesranginginsizefrom40to100nm,whichareessentiallyreleasedfromallcelltypes.Exosomesaresecretedtotheextracellularenvironmentwhenlateendosomalorendosomalmultivesicularbody(MVB)membranesfusewiththeplasmamembrane.Involvedinnum...
