KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program
van Krieken, J. H. J. M × Jung, A Kirchner, T Carneiro, F Seruca, R Bosman, F. T Quirke, P Flejou, J. F Hansen, T. Plato De Hertogh, Gert Jares, P Langner, C Hoefler, G Ligtenberg, M Tiniakos, D Tejpar, Sabine Bevilacqua, G Ensari, A #
Virchows Archiv vol:453 issue:5 pages:417-431
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.