Enzymes involved in tumor-driven angiogenesis: A valuable target for anticancer therapy.

Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman's initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, anti-vascular endothelial growth factor monoclonal antibodies, such as bevacizumab and ramucirumab, and receptor tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, regorafenib and axitinib) have had a profound impact on the way we treat patients with advanced cancer, providing in some cases unprecedented clinical benefit. The molecular mechanisms underlying tumor-driven angiogenesis have been explored extensively and have unveiled a number of potential clinically relevant targets, including several novel enzymes. In this review, we summarized the current strategies to target tumor-driven angiogenesis through the inhibition of relevant and selected classes of enzymes involved in this process.