Tumor angiogenesis. From bench to bedside.

Starting with the hypothesis of Judah Folkman that tumor growth is angiogenesis dependent, this area of research has a solid scientific foundation. More than 30 years ago, Folkman found a revolutionary new way to think about cancer. He postulated that in order to survive and grow, tumors require blood vessels and that by cutting off the blood supply a cancer could be starved into remission. Several clinical studies have shown a positive correlation between the number of vessels in the tumor, metastasis formation and prognosis. The genetic instability of tumor cells permits the occurrence of multiple genetic alterations that facilitate tumor progression and metastasis, and cell clones with diverse biological aggressiveness may coexist within the same tumor. These two properties allow tumors to acquire resistance to cytotoxic agents. Inhibiting angiogenesis is a major area of therapeutic development for the treatment of cancer. Whereas conventional chemotherapy, radiotherapy and immunotherapy are directed against tumor cells, anti-angiogenic therapy is aimed at the vasculature of a tumor and will either cause total tumor regression or keep tumors in a state of dormancy. Even though numerous compounds inhibit angiogenesis, few of them have proved effective in vivo, and only a couple of agents have been able to induce tumor regression. Bevacizumab is considered to be the first specific angiogenesis inhibitor for clinical oncology.