Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations

Area of Science:

• Oncology
• Urology
• Pharmacology

Background:

• Prostate cancer (PCa) is a hormone-sensitive malignancy.
• Hormonal therapy, including androgen deprivation therapy (ADT), is a cornerstone treatment for advanced PCa.
• Despite initial efficacy, resistance to ADT and subsequent therapies like abiraterone acetate and enzalutamide develops, necessitating alternative treatments.

Purpose of the Study:

• To review current antihormonal therapies for prostate cancer.
• To discuss mechanisms of resistance to established and emerging treatments.
• To highlight novel systemic agents currently in clinical trials for castration-resistant PCa.

Main Methods:

• Literature review of antihormonal therapies in prostate cancer.
• Analysis of resistance mechanisms to androgen deprivation and AR-targeted therapies.
• Overview of ongoing clinical investigations for novel systemic agents.

Main Results:

• Hormonal therapies significantly improve survival in metastatic PCa but resistance is common.
• Castration-resistant PCa remains androgen receptor (AR) driven, with identified resistance mechanisms.
• Numerous novel agents, including androgen synthesis inhibitors, AR inhibitors, and heat shock protein modulators, are under investigation.

Conclusions:

• The molecular heterogeneity of castration-resistant PCa necessitates diverse therapeutic strategies.
• Emerging agents show promise in overcoming resistance to current hormonal treatments.
• Continued research and clinical trials are crucial for advancing PCa therapy.