Angiogenesis inhibitors. Drug selectivity and target specificity

The critical role of angiogenesis in tumor development and progression has long been appreciated. The elucidation of the mechanisms of tumor angiogenesis and the emergence of anticancer drugs targeting the tumor vasculature has been a breakthrough in the treatment of several tumors in the last few years. Several novel molecules are being developed that target different aspects of angiogenesis. This review outlines the principle of anti-angiogenic therapies, illustrates the main mechanisms and complexity of growth signals involved in tumor angiogenesis, its interactions with hypoxia, stroma and tumor microenvironment. It provides a comprehensive review of clinical results obtained with anti-angiogenic agents (VEGF/VEGFR signaling inhibitors, direct angiogenesis inhibitors, vascular disrupting agents) and finally discusses the differences of the several approaches and their limitations due to the emergence of resistance.