Colorectal cancer is an excellent tumor model for evaluating novel therapeutic strategies. Development of a mechanistic understanding of how this cancer develops, spreads, and grows allows a tailored approach to all stages of treatment: prevention, adjuvant treatment, and therapy of advanced disease. We focus on therapy in the advanced disease setting, although progress in this area could lend itself to treatment of early or premalignant disease. In the last 20 years, information has been generated about the intracellular pathways of tumor formation, invasion, and metastasis. As a result, specific molecular processes have been targeted for therapeutic intervention, including cell surface growth factor receptors, proliferation signaling, cell cycling, apo-ptosis, angiogenesis, and matrix metalloproteinases. We review the scientific rationale for recently developed novel therapeutics in colorectal cancer, and the results of clinical trials to date. We also suggest appropriate clinical settings for specific targets and outline future directions of research.
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