Angiogenesis as Therapeutic Target in Metastatic Prostate Cancer - Narrowing the Gap Between Bench and Bedside

Area of Science:

• Oncology
• Cancer Biology
• Translational Medicine

Background:

• Angiogenesis is a critical process in metastatic castration-resistant prostate cancer (mCRPC), making it a target for drug development.
• Despite preclinical promise, direct inhibition of angiogenesis has not improved overall survival (OS) in mCRPC patients.
• Tumor heterogeneity and the specific biological context of prostate cancer (PCa) may explain this discrepancy.

Purpose of the Study:

• To review the current landscape of angiogenesis inhibition in PCa.
• To identify novel therapeutic strategies beyond direct angiogenesis inhibitors.
• To explore the potential of PSMA-targeting therapies for anti-angiogenic effects in PCa.

Main Methods:

• Literature review of preclinical and clinical studies on angiogenesis in PCa.
• Analysis of clinicaltrials.gov for ongoing trials investigating angiogenesis inhibitors in PCa (n=20 as of September 2021).
• Exploration of alternative anti-angiogenic compounds (e.g., Metformin, Curcumin) and PSMA-targeting agents.

Main Results:

• Numerous clinical trials (n=20) are investigating specific angiogenesis inhibitors in PCa.
• Compounds like Metformin and Curcumin are also being explored for their anti-angiogenic properties.
• Prostate-Specific Membrane Antigen (PSMA)-targeting therapies show potential for significant anti-angiogenic effects due to PSMA's presence in tumor vasculature.

Conclusions:

• Directly targeting angiogenesis in mCRPC has not translated to improved OS, necessitating a re-evaluation of strategies.
• Future PCa therapies should consider biomarker-guided stratification and combinatorial approaches.
• PSMA-targeting agents represent a promising avenue with potential dual therapeutic benefits, including anti-angiogenesis.