Abstract
Prostate cancer (PCa), like all other solid tumors, relies on angiogenesis for growth, progression, and the dissemination of tumor cells to other parts of the body. Despite data from in vitro and in vivo preclinical studies, as well as human specimen studies indicating the crucial role played by angiogenesis in PCa, angiogenesis inhibition in clinical settings has not shown significant benefits to patients, thus challenging the inclusion and usefulness of antiangiogenic agents for the treatment of PCa. However, one of the apparent reasons why these antiangiogenic agents failed to meet expectations in PCa can be due to the choice of the antiangiogenic agents, because the majority of these drugs target vascular endothelial growth factor-A (VEGFA) and its receptors. The other relevant causes might be inappropriate drug combinations, the duration of treatment, and the method of endpoint determination. In this review, we will first discuss the role of angiogenesis in PCa growth and progression. We will then summarize the different angiogenic growth factors that influence PCa growth dynamics and review the outcomes of clinical trials conducted with antiangiogenic agents in PCa patients and, finally, critically assess the current status and fate of antiangiogenic therapy in this disease.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer in the United States and the second major cause of cancer-related death in men [1]
There is substantial evidence regarding the critical role of angiogenesis in the progression of PCa, with studies reporting correlations between expressions of angiogenic markers, Gleason scores, metastatic disease progression, and clinical outcomes [23,25,32,33,34,35]
Several studies have demonstrated the efficacies of antiangiogenic agents in preclinical PCa models [23,25]
Summary
Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer in the United States and the second major cause of cancer-related death in men [1]. Advancement of clinical research over the last two decades, along with the approval of several targeted and immunomodulatory agents, together with chemotherapeutic agents such as docetaxel, prednisone, and mitoxantrone, have substantially changed the treatment landscape of metastatic CRPC (mCRPC). These agents have shown significant benefits to a percentage of patients, these benefits are short-lived [9,10,11,12,13]. Based on our current knowledge and relevant reports in literature, we will here discuss the importance of angiogenesis in PCa and the relevance of antiangiogenic strategies for the management of this disease
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