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

Abstract

Angiogenesis in metastatic castration-resistant prostate cancer (mCRPC) has been extensively investigated as a promising druggable biological process. Nonetheless, targeting angiogenesis has failed to impact overall survival (OS) in patients with mCRPC despite promising preclinical and early clinical data. This discrepancy prompted a literature review highlighting the tumor heterogeneity and biological context of Prostate Cancer (PCa). Narrowing the gap between the bench and bedside appears critical for developing novel therapeutic strategies. Searching clinicaltrials.gov for studies examining angiogenesis inhibition in patients with PCa resulted in n=20 trials with specific angiogenesis inhibitors currently recruiting (as of September 2021). Moreover, several other compounds with known anti-angiogenic properties - such as Metformin or Curcumin - are currently investigated. In general, angiogenesis-targeting strategies in PCa include biomarker-guided treatment stratification - as well as combinatorial approaches. Beyond established angiogenesis inhibitors, PCa therapies aiming at PSMA (Prostate Specific Membrane Antigen) hold the promise to have a substantial anti-angiogenic effect - due to PSMA´s abundant expression in tumor vasculature.

Keywords: PCa; PSMA; Prostate adenocarcinoma; TKI; angiogenesis inhibitors; clinical trials; immunotherapy; tumor microenvironment.