The role of adrenal derived androgens in castration resistant prostate cancer

被引：48

作者：

Barnard, Monique ^{[1
]}

Mostaghel, Elahe A. ^{[2
,3
,4
]}

Auchus, Richard J. ^{[5
,6
]}

Storbeck, Karl-Heinz ^{[1
]}

机构：

[1] Stellenbosch Univ, Dept Biochem, Stellenbosch, South Africa

[2] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA

[3] Univ Washington, Dept Med, Seattle, WA USA

[4] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA

[5] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2020年 / 197卷

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

Prostate cancer; Adrenal androgen precursors; 11; beta-hydroxyandrostenedione; 11-oxygenated androgens; 11-ketotestosterone; RECEPTOR SPLICE VARIANTS; ACETATE PLUS PREDNISONE; LONG-TERM SURVIVAL; ABIRATERONE ACETATE; DEPRIVATION THERAPY; HIGH-RISK; PHASE-II; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; 5-ALPHA-REDUCTASE ISOENZYMES; STEROID; 5-ALPHA-REDUCTASE;

D O I：

10.1016/j.jsbmb.2019.105506

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Castration resistant prostate cancer (CRPC) remains androgen dependant despite castrate levels of circulating testosterone following androgen deprivation therapy, the first line of treatment for advanced metstatic prostate cancer. CRPC is characterized by alterations in the expression levels of steroidgenic enzymes that enable the tumour to derive potent androgens from circulating adrenal androgen precursors. Intratumoral androgen biosynthesis leads to the localized production of both canonical androgens such as 5 alpha-dihydrotestosterone (DHT) as well as less well characterized 11-oxygenated androgens, which until recently have been overlooked in the context of CRPC. In this review we discuss the contribution of both canonical and 11-oxygenated androgen precursors to the intratumoral androgen pool in CRPC. We present evidence that CRPC remains androgen dependent and discuss the alterations in steroidogenic enzyme expression and how these affect the various pathways to intratumoral androgen biosynthesis. Finally we summarize the current treatment strategies for targeting adrenal derived androgen biosynthesis.

引用

页数：14

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