Colon cancer angiogenesis and antiangiogenic therapy

Metastatic development is the primary cause of cancer treatment failure and is responsible for most deaths from colorectal cancer. For the majority of patients, by the time primary colorectal cancers are diagnosed, sub-clinical or clinically relevant liver metastases have already occurred. The formation of liver metastases represents a highly selective sequence in which a subpopulation of cells, within a tumour, express genes that allow them to progress through distinct steps and spread to distant organs. Modification of gene expression in these cells leads to transformation, growth, angiogenesis, invasion, dissemination, survival in systemic circulation and attachment in the organ of metastases. Existing therapies directed at metastatic disease of the liver have had minimal impact on outcome. Contemporary treatment regimens are not likely to significantly alter the natural history of liver metastases. Consequently, understanding the molecular and biological mechanisms of colorectal cancer may allow for the development of therapeutic strategies designed to prevent and treat liver metastases. Standard chemotherapy regimens have had only minimal success in effectively treating metastatic colorectal cancer. This review focuses on the molecular and biological mechanisms of colorectal cancer angiogenesis. In addition, this report will evaluate the novel antiangiogenic therapeutic strategies targeting colorectal cancer and hepatic metastases.