The Biology of K-Ras and B-Raf Mutations in Colorectal Cancer |
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Authors: | Yixing Jiang Heath Mackley Hua Cheng Jaffer A. Ajani |
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Affiliation: | 1.Penn State Hershey Cancer Institute,Penn State College of Medicine,Hershey,USA;2.Department of Gastrointestinal Medical Oncology,The University of Texas M.D. Anderson Cancer Center,Houston,USA |
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Abstract: | Ras and Raf proteins are two major players in the MAP kinase pathway. They are crucial downstream regulators of multiple receptor tyrosine kinase-mediated cell growth, transformation, and maintenance of the malignant phenotype in human cancers. Mutations have been identified in K-Ras and B-Raf in patients with colorectal cancer. Clinical studies in colorectal cancers demonstrate that the therapeutic efficacy of cetuximab, a chimeric monoclonal antibody against epidermal growth factor receptor, depends on the presence of wild-type K-Ras. However, mutations in B-Raf do not predict cetuximab resistance. These observations have led to the use of K-Ras as a predictive biomarker, allowing clinicians to direct the therapy of cancer patients based on their K-Ras mutational status. |
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