Colorectal cancer (CRC) is the second-leading cause of cancer deaths in the US and the third most common cancer malignancy annually. Overall prognosis of metastatic CRC is still poor, with five-year survival within 5-8 %. Previousmolecular studies of CRC established several key events in CRC disease progression, including APC inactivation, β;- catenin activation, and activating KRAS and BRAF mutations. More recent development of molecular therapeutics has led to the current use of anti-EGFR monoclonal antibody in targeted therapy of advanced CRC. Also, high-throughput cancer genome mutational analysis and newer second-generation cancer genome sequencing have, in recent years, resulted in a deeper understanding of the genome and of regulation of CRC. Most importantly, improved understanding of the involvement of many of the novel molecular targets in CRC tumorigenesis and tumor progression would engender the development of novel targeted therapeutics to treat the disease. Moreover, studies in molecular determinants of predictive and prognostic biomarkers of targeted therapy would further enable better strategies for the use of targeted therapeutics in preventing or overcoming treatment resistance. In this review, we focus on recent findings and their clinical relevance to actionable molecular targets-insulin-like growth factor-1 receptor (IGF-1R), phosphatase and tensin homolog (PTEN), c-Met and phosphatidylinositol 3-OH kinase (PI3-K)-in CRC personalized cancer therapeutics.
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