Molecular Pathology Laboratory Network

The incidence of KRAS gene mutation in colorectal cancer (CRC) is approximately 35-45%. Identifying patients who will benefit from treatment is vital to ensuring better clinical outcomes as well as determining the best treatment strategies for each patient. Based on annual incidence of new metastatic CRC cases, a savings of more than $604 million for cetuximab alone would result through therapeutic drug stratification based upon KRAS status.

In 2009, the American Society of Clinical Oncology released its first Provisional Clinical Opinion recommending that all patients with CRC being considered for EGFR antagonists should be tested for KRAS gene mutations prior to the initiation of therapy. In addition, the National Comprehensive Cancer Network also updated its guideline recomending KRAS testing on primary tumor or metastasis as a pre-treatment workup for metastatic CRC patients, and also when KRAS gene is not mutated determine BRAF gene status.

BRAF V600 mutation testing identifies the subset of colorectal cancer patients who have normal KRAS gene and do not respond to anti-EGFR therapy. BRAF mutation testing is utilized as an independent predictor of (CRC) patient responsiveness to EGFR inhibitor therapy and to assist with the differentiation of microsatellite instability high (MSI-H) hereditary non-polyposis colon cancer (HNPCC) from sporadic MSI-H CRC.

KRAS Journal Articles

• Siena S et al (2009). Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor - Targeted Therapy in Metastatic Colorectal Cancer. JNCI. 101: 1308-1324
• Allegra C J et al. (2009). ASCO Provisional Clinical Opnion: Testing for KRAS Gene Mutations in Patients with Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy. JCO. 27: 2091-2096 »
• V. Shankaran et al. (2009). Economic implications of Kras testing in metastatic colorectal cancer (mCRC). Gastrointestinal Cancers Symposium. Abstratct No. 298. »
• Lievre A et al. (2007). KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer . Cancer Res 66:3992-3995. »
• Di Fiore F et al. (2007).Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96:1166-1169. »
• De Roock W et al. (2008). KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19:508-515. »
• Lievre A et al. (2008). KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab. J Clin Oncol 26:374-379. »