Angiogenesis in cancer

Abstract

New growth in the vascular network is important since the proliferation, as well as metastatic spread, of cancer cells depends on an adequate supply of oxygen and nutrients and the removal of waste products. New blood and lymphatic vessels form through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. More than a dozen different proteins have been identified as angiogenic activators and inhibitors. Levels of expression of angiogenic factors reflect the aggressiveness of tumor cells. The discovery of angiogenic inhibitors should help to reduce both morbidity and mortality from carcinomas. Thousands of patients have received antiangiogenic therapy to date. Despite their theoretical efficacy, antiangiogeic treatments have not proved beneficial in terms of long-term survival. There is an urgent need for a new comprehensive treatment strategy combining antiangiogenic agents with conventional cytoreductive treatments in the control of cancer.

Figure 1

Angiogenesis is regulated by a balance between activators and inhibitors (a). When tumor tissues require fuel (nutrients and oxygen), angiogenesis is stimulated. However, up-regulation of by the activity of angiogenic activators alone is not sufficient for angiogenesis of the neoplasm. Negative regulators or inhibitors of vessel growth need also to be down-regulated (b).