Targeting CYP17: established and novel approaches in prostate cancer

Area of Science:

• Oncology
• Endocrinology
• Pharmacology

Background:

• Medical castration blocks gonadal testosterone but not all androgen production in prostate cancer.
• Androgen receptor (AR) signaling persists in castration-resistant prostate cancer (CRPC), driven by alternative androgen sources.
• Intratumoral androgen synthesis suggests a potential therapeutic target in CRPC.

Purpose of the Study:

• To review the rationale and implications of targeting CYP17 in CRPC.
• To discuss established and novel CYP17 inhibitors for CRPC treatment.

Main Methods:

• Review of existing literature on androgen biosynthesis and CYP17 inhibition in prostate cancer.
• Focus on CYP17 enzyme's role in androgen synthesis pathway (17alpha-hydroxylase and C(17,20)-lyase activities).
• Examination of clinical development stages for CYP17 inhibitors.

Main Results:

• CYP17 is a key enzyme in the de novo synthesis of androgens in CRPC.
• Inhibiting CYP17 offers a rational therapeutic strategy to block systemic androgen biosynthesis.
• Several CYP17 inhibitors, including ketoconazole, abiraterone acetate, and VN/124-1, are under investigation.

Conclusions:

• Targeting CYP17 is a promising strategy for managing castration-resistant prostate cancer.
• Abiraterone acetate and other CYP17 inhibitors represent important advancements in CRPC therapy.
• Further research and development of CYP17 inhibitors are crucial for improving patient outcomes.