Antiangiogenesis therapy in the treatment of metastatic colorectal cancer.

The process of new blood vessel formation, or angiogenesis, has become an important target for therapeutic intervention in many cancers, including metastatic colorectal cancer (mCRC). The growth and metastasis of primary tumors is dependent upon their ability to acquire and maintain an adequate blood supply; however, angiogenesis in tumors is an irregular process leading to chaotic and hyperpermeable vessels that may result in increased intratumoral pressure and poor exchange of macromolecules and oxygen. It has been hypothesized that inhibition of angiogenesis in tumors can both impair the formation of new tumor blood vessels and possibly 'normalize' the existing tumor vasculature, causing a more efficient delivery of cytotoxic chemotherapies (CTs). Over the last decade, therapies that target vascular endothelial growth factor (VEGF) have become a component of treatment for several cancers. In particular, the combination of bevacizumab with established chemotherapeutic regimens for mCRC has been shown to improve overall and progression-free survival, as well as response rates, over CT alone. Agents that target various members of the VEGF family, as well as signaling by the VEGF receptors and their tyrosine kinase components, are currently under development and evaluation in clinical trials. Integration of these new therapies into the treatment of mCRC will ultimately increase the available therapeutic options for patients. Still, many challenges remain, including identifying and validating relevant biomarkers to guide the optimal use of antiangiogenesis agents.