Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor

Colorectal cancer is a prevalent disease in Western countries. While prevention through screening is the best approach to combat the development of colorectal cancer through the removal of precursor adenomas, many patients present with advanced disease that will require surgery and systemic therapy to improve survival. With reference to systemic therapy, the median survival of patients with metastatic colorectal cancer (those with tumor spread to lymph nodes or distant sites) has improved over the past three decades due to the introduction of 5-fluorouracil (5-FU), its subsequent biomodulation, and the addition other chemotherapeutic agents. There is now evidence that the biology of the colorectal tumor, in addition to the stage of colorectal cancer, may predict response to 5-FU-based therapy. More recently, systemic biological therapies that target signaling processes for tumor growth, such as epidermal growth factor receptor, and vascular endothelial growth factor, are also effective in improving patient survival with metastatic colorectal cancer. The use of a combination of systemic therapies that include chemotherapy and biologic therapy should continue to increase patient survival with metastatic colorectal cancer through appropriately designed clinical trials. Treatments based on the biology of the colorectal tumor also need to be examined through clinical trials.