Angiogenesis inhibitors.

Angiogenesis inhibitors target the neovascular development that is hypothesized to underlie tumor growth. The inhibitors that are undergoing the clinical testing phase can be divided into five categories based on their target activity: 1) drugs that block matrix breakdown; 2) drugs that inhibit endothelial cells directly; 3) drugs that block angiogenesis activators; 4) drugs that inhibit endothelial cell integrins or survival signaling; and 5) drugs with a currently unknown mechanism of action. The properties of these drugs and some specific agents in each class are reviewed in this article. Because growth inhibition rather than tumor shrinkage is expected to be the clinical effect of angiogenesis inhibitors, some of the challenges and potential solutions for clinical trial design are also discussed.