A targeted approach for antiangiogenic therapy of metastatic human colon cancer.

The realization that the growth and spread of tumors are dependent on angiogenesis has created new avenues of research designed to help us to better understand cancer biology and to facilitate the development of new therapeutic strategies. However, the process of angiogenesis consists of multiple sequential and interdependent steps with a myriad of positive and negative regulators of angiogenesis being involved. The survival of tumors and thus their metastases are dependent on the balance of endogenous angiogenic and antiangiogenic factors such that the outcome favors increased angiogenesis. Several growth factors have been identified that regulate angiogenesis in colon cancer; the most important of these is vascular endothelial growth factor. In addition, specific integrins such as alphavbeta3 and alpha5beta1 mediate endothelial cell survival and have been shown to be overexpressed on the endothelium of colon cancer. These angiogenic mediators thus serve as targets for therapy of metastatic colon cancer and have shown promise in preclinical trials.