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Prostate cancer—from steroid transformations to clinical translation

Nature Reviews Urology volume 9, pages 721–724 (2012)Cite this article

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Abstract

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.

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Figure 1: DHT synthesis requires reactions catalyzed by CYP17A1, 3βHSD, 5α-reductase, and 17βHSD isoenzymes.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390, TX, USA

    Kai-Hsiung Chang & Nima Sharifi

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  1. Kai-Hsiung Chang
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Both authors contributed towards researching, discussing, writing, and editing the manuscript.

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Correspondence to Nima Sharifi.

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N. Sharifi has been compensated as a consultant for Janssen.

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Chang, KH., Sharifi, N. Prostate cancer—from steroid transformations to clinical translation. Nat Rev Urol 9, 721–724 (2012). https://doi.org/10.1038/nrurol.2012.175

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