期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 197, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2019.105506
关键词
Prostate cancer; Adrenal androgen precursors; 11 beta-hydroxyandrostenedione; 11-oxygenated androgens; 11-ketotestosterone
资金
- National Research Foundation of South Africa [98886]
- Medical Research Council of South Africa
- Cancer Association of South Africa
- NIH Pacific Northwest Prostate Cancer SPORE [P50 CA97186]
- NIH [P01 CA163227, R01GM086596]
- DOD [W81XWH-15-1-0150, W81XWH-12-1-0208]
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.
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