title: KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.
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.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500, HB, The Netherlands. J.vanKrieken@pathol.umcn.nl
authors.forename: J H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: A
authors.initials: A
authors.lastname: Jung
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: F
authors.initials: F
authors.lastname: Carneiro
authors.forename: R
authors.initials: R
authors.lastname: Seruca
authors.forename: F T
authors.initials: FT
authors.lastname: Bosman
authors.forename: P
authors.initials: P
authors.lastname: Quirke
authors.forename: J F
authors.initials: JF
authors.lastname: Fléjou
authors.forename: T
authors.initials: T
authors.lastname: Plato Hansen
authors.forename: G
authors.initials: G
authors.lastname: de Hertogh
authors.forename: P
authors.initials: P
authors.lastname: Jares
authors.forename: C
authors.initials: C
authors.lastname: Langner
authors.forename: G
authors.initials: G
authors.lastname: Hoefler
authors.forename: M
authors.initials: M
authors.lastname: Ligtenberg
authors.forename: D
authors.initials: D
authors.lastname: Tiniakos
authors.forename: S
authors.initials: S
authors.lastname: Tejpar
authors.forename: G
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: A
authors.initials: A
authors.lastname: Ensari
mesh_terms: D000906:Antibodies / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005060:Europe; D005820:Genetic Testing; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011785:Quality Assurance, Health Care; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000906:Antibodies; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins