Title:Androgen Metabolic Pathway Involved in Current and Emerging Treatment for Men with Castration Resistant Prostate Cancer: Intraprostatic Androgens as Therapeutic Targets and Endocrinological Biomarkers
Volume: 15
Issue: 13
Author(s): Noboru Hara and Tsutomu Nishiyama
Affiliation:
Keywords:
Androgen metabolism, androgen receptor, androgen deprivation therapy, prostate cancer.
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.