Prostate cancer-from steroid transformations to clinical translation

Kai Hsiung Chang, Nima Sharifi

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 17-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.

Original languageEnglish (US)
Pages (from-to)721-724
Number of pages4
JournalNature Reviews Urology
Volume9
Issue number12
DOIs
StatePublished - Oct 2 2012

Fingerprint

Castration
Prostatic Neoplasms
Steroids
Steroid 17-alpha-Hydroxylase
docetaxel
Androgens
Dihydrotestosterone
Androgen Receptors
Hormones
Enzymes
MDV 3100
abiraterone
Therapeutics

ASJC Scopus subject areas

  • Urology

Cite this

Prostate cancer-from steroid transformations to clinical translation. / Chang, Kai Hsiung; Sharifi, Nima.

In: Nature Reviews Urology, Vol. 9, No. 12, 02.10.2012, p. 721-724.

Research output: Contribution to journalArticle

Chang, Kai Hsiung ; Sharifi, Nima. / Prostate cancer-from steroid transformations to clinical translation. In: Nature Reviews Urology. 2012 ; Vol. 9, No. 12. pp. 721-724.
@article{c4f30db8a7184326afef6f25467926ae,
title = "Prostate cancer-from steroid transformations to clinical translation",
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 17-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.",
author = "Chang, {Kai Hsiung} and Nima Sharifi",
year = "2012",
month = "10",
day = "2",
doi = "10.1038/nrurol.2012.175",
language = "English (US)",
volume = "9",
pages = "721--724",
journal = "Nature reviews. Urology",
issn = "1759-4812",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Prostate cancer-from steroid transformations to clinical translation

AU - Chang, Kai Hsiung

AU - Sharifi, Nima

PY - 2012/10/2

Y1 - 2012/10/2

N2 - 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 17-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.

AB - 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 17-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.

UR - http://www.scopus.com/inward/record.url?scp=84871074337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871074337&partnerID=8YFLogxK

U2 - 10.1038/nrurol.2012.175

DO - 10.1038/nrurol.2012.175

M3 - Article

VL - 9

SP - 721

EP - 724

JO - Nature reviews. Urology

JF - Nature reviews. Urology

SN - 1759-4812

IS - 12

ER -