Thus, determination of KRAS mutation status in these tumors is critical when evaluating a patient for anti-EGFR therapy. The American Society of Clinical Oncology (ASCO) has further recommended that all patients with metastatic colorectal cancer, for whom EGFR antagonists are being considered,

should be specifically tested for KRAS mutational status at codons 12 and 13. Current guidelines in the US state, that patients with metastatic CRC being considered for EGFR-targeted therapies should be tested for KRAS and BRAF mutations (53) Data from the CRYSTAL trial suggest that BRAF mutations are also indicative Inhibitors,research,lifescience,medical of poor prognosis and the National Comprehensive Cancer Network (NCCN), Colon Cancer Guideline Update 2010 states that testing for mutations in BRAF should occur when KRAS testing indicates KRAS wild type, to avoid exposing patients to ineffective drugs, exposure to unnecessary drug toxicities, and expedite the use of the best available alternative Inhibitors,research,lifescience,medical therapy (54). High-resolution melting (HRM) is a recently developed Inhibitors,research,lifescience,medical technique that shows great potential for scanning germline and somatic mutations (55). Also, another recent study described HRM assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using

formalin-fixed paraffin embedded samples, Inhibitors,research,lifescience,medical which proved HRM as a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples (56). BRAF mutations are now increasingly being investigated in metastatic colorectal cancer. KRAS mutation analysis may be considered medically necessary to predict no response to anti-EGFR monoclonal

antibodies Cetuximab and Panitumumab in the treatment of metastatic, unresectable, or advanced colorectal cancer. BRAF mutation analysis is considered investigational for all indications, including, but not limited to, predicting Inhibitors,research,lifescience,medical no response to anti-EGFR monoclonal antibodies Cetuximab and Panitumumab in the treatment of metastatic, unresectable, or advanced colorectal cancer. KRAS and BRAF mutation analyses using PCR methodology 17-DMAG (Alvespimycin) HCl are commercially available as laboratory-developed tests. Such tests are regulated under the Clinical Laboratory Improvement Amendments (CLIA). Premarket approval from the U.S. Food and Drug Administration (FDA) is not required when the assay is performed in a laboratory that is licensed by CLIA for high-complexity testing. Factors affecting the efficacy of MoAbs Cetuximab In CRC patients other than BRAF, KRAS mutations Mutated BRAF tumors (approximately 10%) add algebraically to those carrying KRAS mutations (35% to 45%), thus further empowering the selection of patients eligible for Cetuximab/selleck compound Panitumab treatment.