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1、MINIREVIEWBritishJournalofCancer(2014),1–6
2、doi:10.1038/bjc.2014.268Keywords:prostatecancer;androgenmetabolism;androgenreceptor;abirateroneacetate;enzalutamide;hormones;enzymes;steroidsAndrogenmetabolisminprostatecancer:frommolecularmechanismstoclinicalconseque
3、nces1,42,4,1,2,3K-HChang,CEErcoleandNSharifi*12DepartmentofCancerBiology,LernerResearchInstitute,ClevelandClinic,Cleveland,OH,USA;DepartmentofUrology,3GlickmanUrologicalandKidneyInstitute,ClevelandClinic,Cleveland,OH,USAandDepartmentofSolidTumorOncology,Taussi
4、gCancerInstitute,ClevelandClinic,Cleveland,OH,USADespiteourmostvigorousefforts,prostatecancerremainsthesecondleadingcauseofcancerdeathinmen.Understandingtheintricaciesofandrogenmetabolismisvitaltofindingtherapeutictargets,particularlywithprogressionofadvancedp
5、rostatecancerafterinitialhormonetherapy,whereadrenalprecursorsareinvolved.Suchisthecasewithcastration-resistantprostatecancer,whereadrenalandrogens,forexample,dehydroepiandrosterone,areasourceforintratumouralsynthesisofdihydrotestosterone.Asprostatecancerprogr
6、esses,androgenmetabolismchangesduetoalteredexpressionofsteroidogenicenzymesandmutationsinthecomponentsofthesteroidogenicmachinery.Thesealterationssustaindiseaseandallowprogression;mechanistically,theymayalsoenabledevelopmentofhormonetherapyresistance.Withthede
7、velopmentoftheneweragents,abirateroneacetateandenzalutamide,effortshavebeenmadetobetterdefinethebasisforresponseandresistance.Thisworkcanbecarriedoutincelllines,animalmodels,aswellaswithexvivoanalysisoftissuesobtainedfrompatients.Effortstofurtherelucidatethefi
8、nerdetailsofthesteroidogenicpathwayarenecessarytomovetowardacurativeparadigmforpatientswithlocaliseddiseaseathighriskforrecurrence.Prostatecanceristhemostcommonnon-skinmalignancyandtheenzalutamide.Abirateroneacetateblocksadrenalandrogensecondleadingcauseofcanc
9、erdeathinmen(Siegeletal,2013).productionbyinhibitingCYP17A1activitytosuppresstumourLocalisedprostatetumoursarepotentiallycurablebyradiationorgrowthandsoleadstoextendedsurvivalforpa
