Author:

Keywords:

colorectal carcinoma, anti-egfr therapy, kras mutation testing, practice guidelines, quality assurance, growth-factor-receptor, k-ras mutations, mismatch repair deficiency, cetuximab shows activity, gene copy number, cancer patients, lung-cancer, molecular-mechanisms, clinical-response, point mutations, Science & Technology, Life Sciences & Biomedicine, Pathology, Colorectal carcinoma, Anti-EGFR therapy, KRAS mutation testing, Practice guidelines, Quality assurance, GROWTH-FACTOR-RECEPTOR, K-RAS MUTATIONS, CETUXIMAB SHOWS ACTIVITY, CANCER PATIENTS, MOLECULAR-MECHANISMS, CLINICAL-RESPONSE, DNA MUTATIONS, LUNG-CANCER, STOOL DNA, COLON, Antibodies, Colorectal Neoplasms, ErbB Receptors, Europe, Genetic Testing, Humans, Point Mutation, Predictive Value of Tests, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), Quality Assurance, Health Care, ras Proteins, 1103 Clinical Sciences, 3202 Clinical sciences

Abstract:

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.