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.
Highlights
The biological context of angiogenesis and prostate cancer (PCa) inspired a plethora of research, in metastatic PCa and in castration-resistant disease (CRPC), the clinical stage in which the majority of clinical trials on angiogenesis inhibition was performed [1]
There has been a fair amount of research to try to analyze the mechanisms of progression to CRPC, which is the lethal phenotype of metastatic PCa – and current evidence suggest a function of Challenges of Angiogenesis Inhibition in Prostate Cancer clonal selection and adaptation by androgen receptor (AR)dependent and independent mechanisms [4]
PCa treatment has rapidly developed towards precision oncology by addressing two novel target pathways: DNA repair and Prostate-specific membrane antigen (PSMA)-related signaling
Summary
The biological context of angiogenesis and prostate cancer (PCa) inspired a plethora of research, in metastatic PCa and in castration-resistant disease (CRPC), the clinical stage in which the majority of clinical trials on angiogenesis inhibition was performed [1]. Metastatic PCa is an androgen-driven and -dependent cancer [2], with androgen deprivation therapy (ADT) being the primary treatment. There has been a fair amount of research to try to analyze the mechanisms of progression to CRPC, which is the lethal phenotype of metastatic PCa – and current evidence suggest a function of Challenges of Angiogenesis Inhibition in Prostate Cancer clonal selection and adaptation by androgen receptor (AR)dependent and independent mechanisms [4]. For PSMA, strategies include radioligand therapy as a theragnostic approach performed by nuclear medicine specialists [16]
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