Development of Novel Targeted Agents in the Treatment of Metastatic Colorectal Cancer

Colorectal cancer (CRC) remains the second most common cause of cancer death and third most common form of cancer in men and women. Although the incidence and mortality of CRC have been declining over the past 2 decades in the United States, nearly 140,000 new cases and 51,000 deaths were still estimated to occur in 2010.1 These decreases have resulted primarily from earlier detection of premalignant colorectal polyps through CRC screening and to a lesser degree from adjuvant chemotherapy. Four cytotoxic chemotherapy drugs and 3 biologic agents have been approved by the US Food and Drug Administration (FDA) for CRC, but the contribution of each has been incremental and long-term survival of advanced disease remains poor. In addition, optimal populations for treatment with these agents remain to be fully characterized. Although the field of drug development in CRC was stagnant during a period of numerous large trials with approved agents, multiple new agents are currently in development. This review discusses molecular pathways and novel targeted agents in the treatment of CRC.