Angiogenesis inhibitors - New agents in cancer therapy

Tumours that do not develop a blood supply cannot grow larger than 1 to 2mm (3). The growth of a tumour blood supply, called angiogenesis, is a complex process that greatly increases the likelihood of metastatic spread and agg ressive tumour behaviour. Molecular processes involved in angiogenesis incl ude stimulation of endothelial growth by tumour cytokine production (vascul ar 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 ta rgeted by several new types of agents broadly classified as angiogenesis in hibitors. Additionally, endogenous angiogenesis inhibitors have been discov ered and one of them, endostatin, is currently undergoing clinical trials. The unique targets of these drugs make them distinct from traditional cytot oxic chemotherapeutic agents. Unlike cytotoxic chemotherapy, in which the b iological effect of the drug produces the anti-tumour effect as well as the toxic effect, angiogenesis inhibitors may produce their biological effect independently of the toxic effect. This fact raises important questions amo ng clinical investigators as to what is the most effective way to administe r these drugs and monitor their effects. This paper details some of the sci entific evidence making angiogenesis an important therapeutic target as wel l as issues regarding the structure of clinical trials with these new antic ancer agents.