Novel molecular targets for the therapy of castration-resistant prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) progression is driven by multiple molecular mechanisms.
• Recent therapeutic advances include abiraterone acetate, sipuleucel-T, cabazitaxel, and denosumab, highlighting key pathways like androgen inhibition and immunotherapy.
• Emerging agents like MDV-3100 and radium-223 further emphasize the importance of targeting specific molecular pathways.

Purpose of the Study:

• To review the next generation of molecular targets for treating mCRPC.
• To identify promising novel agents and pathways currently under investigation.

Main Methods:

• A comprehensive literature search of Medline databases was conducted for articles published up to October 18, 2011.
• Search terms included "metastatic castration-resistant prostate cancer," "targeted therapy," "biologic agents," and "immunotherapy."
• Proceedings from major oncology and urology conferences over the preceding five years were also reviewed, focusing on drugs in clinical trials.

Main Results:

• Analysis of prospective trials and preclinical data revealed multiple molecular drivers in mCRPC.
• Key pathways under investigation include androgen signaling, immunoregulatory pathways, Src, Met, clusterin, and angiogenesis.
• Several novel agents targeting these pathways are in active clinical development.

Conclusions:

• mCRPC is characterized by diverse molecular drivers, necessitating targeted therapeutic approaches.
• Ongoing phase 3 trials are evaluating novel agents like MDV3100, TAK700, ipilimumab, Prostvac-VF-TRICOM, dasatinib, cabozantinib, custirsen, aflibercept, and tasquinimod.
• The identification of novel molecular targets presents significant opportunities to improve outcomes for patients with mCRPC.