Development of Rationally Designed, Target-Based Agents for the Treatment of Advanced Colorectal Cancer

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Although there have been several recent additions to the conventional armamentarium used to treat patients with advanced colorectal cancer, principally as a result of the development of selective and nonselective pharmacologic agents and antibodies, the general outcome of patients with advanced disease is still poor. However, a greater understanding of cancer biology, as well as major advances in biotechnology, is beginning to identify and characterize molecular aberrations that are common in patients with colorectal cancer.These advances have resulted in the development of a wide range of rationally designed, target-based anticancer therapeutic agents, which, by virtue of their selectivity, would be expected to produce less nonspecific toxicity and therefore higher therapeutic indices compared with nonspecific cytotoxic agents. This review will discuss several novel targets and therapeutic agents, particularly those designed to interrupt aberrant signal transduction and apoptotic processes. It will also emphasize the complexity of these systems and the need to incorporate novel clinical development paradigms based on a thorough scientific understanding of these targets.

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