K-Ras – pro
One of the major recent advances in the field of colorectal cancer has been the identification of K-Ras mutations. K-Ras mutation determines colorectal cancer’s responsiveness to Erbitux and panitumumab. The discovery that metastatic colon cancer tumors express the KRAS gene in 2 forms — mutated and wild-type — has effectively split colon cancer into 2 separate diseases. About 40% of patients with metastatic colon cancer have tumors with a mutated form of the KRAS gene, and these patients are unlikely to respond to treatment with cetuximab and panitumumab. The other patients with the normal, or wild-type, KRAS genes are likely to respond to these drugs. Testing for KRAS gene mutations has been added to ASCO and the updated National Comprehensive Cancer Network (NCCN) clinical-practice guidelines for colon cancer. The new guidelines stipulate that only patients whose tumors have the wild-type (normal) KRAS genes should receive treatment with the epidermal growth-factor receptor (EGRF) inhibitors cetuximab and panitumumab. It is supported by NCCN COL-5 in metastatic colon cancer.
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nccn, colon, COL-5
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Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26(10):1626-34.
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Van Cutsem E, Lang I, D’haens G et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. J Clin Oncol 2008; 26(15 suppl):abstract 2.
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Linardou H, Dahabreh IJ, Kanaloupiti D et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncology 2008 Sept 17. [Epub ahead of print].
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Lievre A, Bachet JB, Boige V et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008; 26(3):374-9.