Targeting Angiogenesis in Cancer Treatments: Where do we Stand?

作者：Nenad T. Petrovic · 发表于：Journal of Pharmacy & Pharmaceutical Sciences · 年份：2016 · DOI：10.18433/j30033 · 被引用次数：48 · 研究领域：Angiogenesis and VEGF in Cancer、Cancer Mechanisms and Therapy、Cancer, Lipids, and Metabolism

Since early seventies of the twentieth century, through seminal work of Judah Folkman, angiogenesis, the process of new blood vessel sprouting from the existing vasculature, was recognized as a necessary part of wound healing, development of placenta, tissue growth and regeneration as well as cancer progression. This process is induced by low tissue oxygenation and it is a crucial prerequisite for rapid tissue growth, providing proper oxygen supply and removal of toxic metabolites. Suppression of angiogenesis as a way of slowing down tumor progression continues to be one of the most important areas of cancer research. The angiogenic process is relatively complex and it is regulated by numerous pro- and anti-angiogenic factors. Intensive research in the last twenty years resulted in identification of more than 300 angiogenesis inhibitors, a trend that is expected to continue. Unfortunately, most of these treatments have demonstrated unacceptable toxicities or failed to show activity in clinical studies. Although not yet completely understood, the complex process of tumor angiogenesis involves highly regulated orchestration of multiple activating and inhibiting factors. Vascular endothelial growth factor (VEGF) and its cognate receptors appear to play a central role in angiogenesis activation. Thus, initial efforts to develop anti-angiogenic treatments focused largely on inhibiting VEGF action. Such approaches, however, often lead to transient responses due to multiple pathways...