Androgen metabolic pathway involved in current and emerging treatment for men with castration resistant prostate cancer: intraprostatic androgens as therapeutic targets and endocrinological biomarkers.

Abstract:

:Androgen and androgen receptor (AR) play a critical role in the development of prostate cancer. Androgen deprivation therapy (ADT) has become the therapeutic mainstay for patients with metastatic prostate cancer. ADT can reduce the serum testosterone level from the normal range between 500 and 600 ng/dl to the castrate level. Following surgical castration, the serum testosterone level decreases to less than 20 ng/dL (0.69 nmol/L) in about three quarters of the patients. Although insufficient suppressions of the serum testosterone level following ADT have not been well recognized to date, the failure in achieving the castrate level of testosterone may have an adverse impact on survival in men with prostate cancer. Although circulating testosterone levels following castration do not necessarily reflect the amount of intraprostatic testosterone or dihydrotestosterone, testosterone during ADT mainly derives from intratumorally synthesized precursors and adrenal androgens. The advent of new agents represented by abiraterone acetate and enzalutamide, which target adrenal or intraprostatic androgen biosynthesis and AR signaling, respectively, has retrieved interest in testosterone levels during ADT. We critically reviewed androgen metabolism and its significance in prostate cancer biology and treatment to promote their better understanding and management of men with prostate cancer.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Hara N,Nishiyama T

doi

10.2174/1389450115666141024114736

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

1215-24

issue

13

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-63028

journal_volume

15

pub_type

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