The role of targeted therapy in the treatment of colorectal cancer.

Recent years have brought significant advances in the treatment of metastatic colorectal cancer. Combination regimens with standard chemotherapeutic agents have extended survival to nearly 2 years, and recent studies suggest that chemotherapy-free intervals may be feasible in some patients without compromising survival outcomes. The most significant recent progress has centered on the use of targeted biologic therapies. The first targeted agent to show a significant benefit in metastatic colorectal cancer was bevacizumab. This monoclonal antibody is directed against vascular endothelial growth factor, a molecule known to be involved in the angiogenic process that is central to cancer growth and metastasis. In clinical trials, bevacizumab has improved survival when added to multiple chemotherapy regimens. The second targeted agent to be approved for colorectal cancer is the monoclonal antibody cetuximab, which is directed against the epidermal growth factor receptor, another key mediator of cancer growth. Cetuximab has been shown to increases the efficacy of irinotecan in irinotecan-refractory patients, indicating that cetuximab may make tumors more sensitive to chemotherapeutic agents. Bevacizumab and cetuximab continue to be evaluated alone as maintenance therapy and in combination in different settings to determine their optimal use in colorectal cancer. Additional targeted agents are also being developed and are showing promise in clinical trials.