Document Detail


Prostate cancer-from steroid transformations to clinical translation.
MedLine Citation:
PMID:  23027067     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The survival benefit conferred by two hormonal agents in phase III trials has clinically validated the long suspected and now widely recognized phenomenon of castration-resistant prostate cancer (CRPC) hormone dependence. Abiraterone inhibits steroid 17α-hydroxylase/17,20-lyase (CYP17A1) and blocks androgen synthesis, whereas enzalutamide directly binds and antagonizes the androgen receptor. Both agents are highly effective against CRPC and significantly prolong survival following docetaxel treatment. However, this clinical validation of the androgen pathway has led to questions regarding the fundamental mechanisms of CRPC, as well as resistance to abiraterone and enzalutamide. Our understanding of the predominant steroid transformation pathways that lead to dihydrotestosterone synthesis in CRPC is evolving. The role of steroidogenesis in the development of resistance to abiraterone and enzalutamide remains uncertain. The specific roles of candidate enzyme targets in the development of resistance to these agents must be defined if we are to identify novel targets for improved pharmacologic therapies.
Authors:
Kai-Hsiung Chang; Nima Sharifi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-02
Journal Detail:
Title:  Nature reviews. Urology     Volume:  -     ISSN:  1759-4820     ISO Abbreviation:  Nat Rev Urol     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101500082     Medline TA:  Nat Rev Urol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
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