Steroidogenesis Inhibitors Alter But Do Not Eliminate Androgen Synthesis Mechanisms During Progression to Castration-Resistance in LNCaP Prostate Xenografts
April 2009
in “
The Journal of Steroid Biochemistry and Molecular Biology
”
steroidogenesis inhibitors androgen synthesis castration-resistant prostate cancer CRPC LNCaP prostate xenografts adrenal steroid precursors cholesterol progesterone CYP17A1 SRD5A2 dihydrotestosterone DHT androgen blockers prostate cancer adrenal steroids CYP17A1 inhibitors 5-alpha reductase inhibitors
TLDR Steroidogenesis inhibitors change but don't stop androgen production in prostate cancer.
The study investigated the effects of steroidogenesis inhibitors on androgen synthesis in castration-resistant prostate cancer (CRPC) using LNCaP cells and xenograft tumors. It was found that inhibitors targeting CYP17A1 and SRD5A2 significantly altered but did not eliminate androgen synthesis from progesterone. CRPC tumors adapted to synthesize dihydrotestosterone (DHT) through alternative mechanisms despite the presence of these inhibitors. Tumors immediately after castration were less efficient at metabolizing progesterone compared to CRPC tumors. The study suggested that targeting the androgen axis might be most effective when tumors are least efficient at synthesizing androgens. Further studies in humans were recommended to validate these findings.
