Prostate cancer progression after androgen deprivation therapy. mechanisms of castrate resistance and novel therapeutic approaches

《Prostate cancer progression after androgen deprivation therapy. mechanisms of castrate resistance and novel therapeutic approaches》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、OPENOncogene(2013)32,5501–5511&2013MacmillanPublishersLimitedAllrightsreserved0950-9232/13www.nature.com/oncREVIEWProstatecancerprogressionafterandrogendeprivationtherapy:mechanismsofcastrateresistanceandnoveltherapeuticapproachesTKarantanos,PGCornandTCThompsonP

2、rostatecanceristhesecond-leadingcauseofcancer-relatedmortalityinmeninWesternsocieties.Androgenreceptor(AR)signalingisacriticalsurvivalpathwayforprostatecancercells,andandrogen-deprivationtherapy(ADT)remainstheprincipaltreatmentforpatientswithlocallyadvancedandme

3、tastaticdisease.AlthoughamajorityofpatientsinitiallyrespondtoADT,mostwilleventuallydevelopcastrateresistance,definedasdiseaseprogressiondespiteserumtestosteronelevelsofo20ng/dl.TherecentdiscoverythatARsignalingpersistsduringsystemiccastrationviaintratumoralproduc

4、tionofandrogensledtothedevelopmentofnovelanti-androgentherapiesincludingabirateroneacetateandenzalutamide.Althoughtheseagentseffectivelypalliatesymptomsandprolonglife,metastaticcastration-resistantprostatecancerremainsincurable.Anincreasedunderstandingofthemecha

5、nismsthatunderliethepathogenesisofcastrateresistanceisthereforeneededtodevelopnoveltherapeuticapproachesforthisdisease.Theaimofthisreviewistosummarizethecurrentliteratureonthebiologyandtreatmentofcastrate-resistantprostatecancer.Oncogene(2013)32,5501–5511;doi:10

6、.1038/onc.2013.206;publishedonline10June2013Keywords:castrate-resistantprostatecancer;ADT;alternativepathwaysINTRODUCTIONTheARisbelievedtoremainactiveinCRPC,andseveralnewThemainstayoftherapyforpatientswithlocallyadvancedstrategiestoinhibitARsignalinghaverecently

7、beendeveloped.prostatecancer,metastaticprostatecancerandbiochemicallyAbirateroneacetate(Zytiga;JanssenBiotech,Inc.Horsham,PA,recurrentdiseaseafterfailureoflocalizedtreatmentsisUSA)isanFDA-approvedinhibitorofandrogenbiosynthesis,androgen-deprivationtherapy(ADT)wi

8、thgonadropin-releasingwhichblockscytochromeP450-c17(CYP17),leadingtosuppres-1hormoneanalogsandanti-androgens.Gonadropin-releasingsionofandrogensderivedfromtheadrenalg