Novel agents in the treatment of metastatic colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer death in the United States. Research has led to an explosion of knowledge into the molecular basis of CRC in the past decades. Numerous receptors and intracellular proteins have been identified and implicated in the growth and progression of metastatic CRC, thus creating novel targets for drug development. Many agents are under development and have begun to enter early and even later-stage clinical trials. Results of these agents have demonstrated some encouraging activity but in a small number of patients. Research into predictive biomarkers aims to select the patients who may benefit from these novel agents. This review will address several of these promising new agents, their potential relevance to CRC, results from early clinical studies, and their incorporation into future and ongoing CRC clinical trials. Clearly, there is an urgent need for new agents in this disease, but as we learned from the experience with epidermal growth factor receptor-targeted antibodies, patient selection will be increasingly be required for individualized therapy to become a reality in CRC.