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.
No recommendations on when to perform K-Ras testing are available. Some advocate performing it at initial diagnosis so as to be ready for future possible use of EGFR antagonists. Others argue that a test should only be performed when such treatment is considered, usually in 2nd or 3rd line.
In the future K-Ras may turn out to be a prognostic factor but at this time it is only useful in later lines of therapy.
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