Angiogenesis inhibitors. New agents in cancer therapy.

Tumours that do not develop a blood supply cannot grow larger than 1 to 2mm3. The growth of a tumour blood supply, called angiogenesis, is a complex process that greatly increases the likelihood of metastatic spread and aggressive tumour behaviour. Molecular processes involved in angiogenesis include stimulation of endothelial growth by tumour cytokine production (vascular endothelial growth factor), degradation of extracellular matrix proteins by metalloproteinases, and migration of endothelial cells mediated by cell membrane adhesion molecules called integrins. These processes are being targeted by several new types of agents broadly classified as angiogenesis inhibitors. Additionally, endogenous angiogenesis inhibitors have been discovered and one of them, endostatin, is currently undergoing clinical trials. The unique targets of these drugs make them distinct from traditional cytotoxic chemotherapeutic agents. Unlike cytotoxic chemotherapy, in which the biological effect of the drug produces the antitumour effect as well as the toxic effect, angiogenesis inhibitors may produce their biological effect independently of the toxic effect. This fact raises important questions among clinical investigators as to what is the most effective way to administer these drugs and monitor their effects. This paper details some of the scientific evidence making angiogenesis an important therapeutic target as well as issues regarding the structure of clinical trials with these new anticancer agents.