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1、ReviewTargetingmetastaticcastration-resistantprostatecancer:mechanismsofprogressionand1.Introductionnovelearlytherapeutic2.NewevidencesofmolecularmechanismsduringmCRPCapproachesprogression3.NoveltreatmentsinmCRPCVittoreCereda†,VincenzoFormica,GioiaMassimiani,Li
2、viaTosetto&4.ConclusionMarioRoselli5.ExpertopinionUniversityofRome‘TorVergata’,TorVergataClinicalCenter,DepartmentofSystemsMedicine,MedicalOncology,Rome,ItalyIntroduction:Advancesinclinicalresearchhaveledtoofficialapprovalofseveralnewtreatmentsformetastaticpros
3、tatecancerinthelastthreeyears:sipuleucel-T,cabazitaxel,abirateroneacetate,radium-223andenzalutamide.AlthoughtheseagentshaveallbeenshowntoimproveoverallsurvivalinrandomizedPhaseIIItrials,metastaticcastration-resistantprostatecancer(mCRPC)remainsincurable.Areasco
4、vered:First,thereviewsummarizesthecurrentliteratureonthebiol-ogyofmCRPC.Theemergingdataareincreasingourunderstandingofthemechanismsthatunderliethepathogenesisofcastrateresistanceandwherefuturetreatmentmightbeheaded.Inthesecondpartofthereview,theauthorsassessthe
5、futuredirectionsindiseasetherapy.Indeed,novelselectedtherapeuticapproaches,includingnovelagentsandcombinatorialtherapies,areshowingpromisingearlyresults.Expertopinion:Targetingdifferentmolecularpathwaysincombinationwithimmunotherapycanbeapromisingdirectioninmet
6、astaticcastrationprostatecancertreatment.However,severalchallengesstillexistincludingelucidatingtheoptimaluseandsequencingofthesenewagents.Therearealsochallengesinboththedesignandtheinterpretationoftheresultsfromclinicaltrials.Keywords:androgenreceptor,castrati
7、onresistance,combinatorialtherapy,immunotherapy,neoangiogenesis,prostatecancerExpertOpin.Investig.Drugs[EarlyOnline]1.IntroductionProstatecanceristhemostcommonnoncutaneousmalignancyamongNorthAmericanandEuropeanmenandthesecondleadingcauseofmalecancer-relateddeat
8、hafterlungcancer[1,2].Suppressionofgonadalandrogens(withluteinizing-hormone-releasinghormone[LHRH]analogs/antagonists)remainsthefirstlineoftherapyforpatientswhorelapsefollow
