Regulation of vascular endothelial growth factor in prostate cancer

Prostate cancer (PCa) is the most common malignancy affecting men in the western world. While radical prostatectomy and radiation therapy can successfully treat a majority of patients, up to ~30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Whilst such androgen deprivation therapies (ADT) are effective initially, the duration of response is typically ≤24 months. While ADT and taxane based chemotherapy have delivered survival benefits, metastatic prostate cancer remains incurable. Therefore it is essential to establish the cellular and molecular mechanisms which enable localized prostate cancers to invade and disseminate. It has long been accepted that metastases requires angiogenesis. In this review we will examine the essential role for angiogenesis in PCa metastases and in particular we will focus on current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We will highlight recent advances in understanding the role of VEGF in regulating interaction of cancer cells with tumor-associated immune cells during metastatic process of PCa. We will summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in prostate cancer cells and will outline the molecular insights obtained from pre-clinical animal models of prostate cancer. Finally we will summarize the current state of anti-angiogenesis therapies for PCa and how existing therapies impact on VEGF signalling. . (Less)