Inhibition of angiogenesis.

The concept of antiangiogenic therapy was first proposed in the early 1970s as a method of restricting tumor growth by inhibiting angiogenesis. In subsequent years sufficient knowledge about the process of angiogenesis itself was obtained so that it is now possible to begin to develop antiangiogenic therapy for clinical use. At least three strategies are feasible: (i) inhibition of release of angiogenic molecules from tumor cells; (ii) neutralization of angiogenic molecules that have already been released; and (iii) inhibition of vascular endothelial cells from responding to angiogenic stimulation. Most of the angiogenic inhibitors that have been discovered at the time of writing, directly interfere with the ability of endothelial cells to form new capillary blood vessels. Antiangiogenic activity is a newly found property of alpha-interferon. Although alpha-interferon is a relatively weak angiogenesis inhibitor in comparison to others, it has been very successful in the treatment of life-threatening hemangiomas in children. Early clinical experience with this first angiogenesis inhibitor to reach clinical trial, indicates that optimal antiangiogenic therapy in the future is likely to be based on the long-term use of inhibitors with low toxicity, and with little chance of inducing drug-resistance. It is apparent that different types of angiogenesis inhibitor may be administered together and that these compounds may also be administered to cancer patients as adjuncts to conventional chemotherapy. It is important to recognize that tumor vasculature has other properties besides angiogenesis, which make it a potential specific target for anti-cancer therapy.