Angiogenesis and its role in colorectal tumor and metastasis formation

Advances in our comprehension of cancer biology and metastasis formation have led to the development of new therapeutic approaches that target tumor biology. The survival and establishment of metastatic lesions depend on a shift in the normal balance of key regulatory factors in favor of angiogenesis. Although a number of these factors have been identified, the most potent regulator of angiogenesis is vascular endothelial growth factor (VEGF). In phase I trials, targeting VEGF with single-agent therapy did not produce clinical benefit for patients, despite promise in preclinical trials. However, the recent data showing that anti-VEGF therapy can enhance the effects of chemotherapy demonstrate the utility in targeting angiogenic factors as a component of antineoplastic regimens. A better understanding of the functions of VEGF allows the development of new hypotheses with regard to its mechanism of action. This article will highlight what is known about colorectal cancer angiogenesis, and will discuss how therapy targeting VEGF may enhance the effects of chemotherapy (and radiation therapy). © 2004 Elsevier Inc. All rights reserved.