Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology

Purpose of Review: Targeting specific steroidogenic enzymes effectively reduces testosterone synthesis, leading to significant antitumor effects in prostate cancer. However, these treatments also disrupt complex, interconnected pathways with systemic physiological consequences, particularly impacting the adrenal gland and the renin-angiotensin-aldosterone system. This review highlights key considerations for managing patients undergoing treatment with androgen biosynthesis inhibitors.

Recent Findings: In prostate cancer treatment, targeting CYP17A1, a crucial enzyme in androgen biosynthesis, is a well-established approach. Recently, attention has shifted to targeting CYP11A1, a gatekeeper enzyme in steroidogenesis responsible for converting cholesterol to pregnenolone, the initial step in steroid hormone production. Emerging studies show that ODM-208, a CYP11A1 inhibitor, exhibits antitumor effects in prostate cancer. Although this strategy is promising, targeting CYP11A1 may lead to significant downstream effects, such as long-term adrenal insufficiency and potential cardiovascular dysregulation, due to the suppression of the entire adrenal cortex.

Summary: Androgen biosynthesis inhibitors can have wide-ranging systemic effects. Achieving a balance between effective prostate cancer management and a deeper understanding of the mechanisms behind potential side effects is crucial. This approach will help maximize antitumor benefits ODM208 while minimizing treatment-related adverse effects.