KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.
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.
van Krieken
J H J M
JH
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500, HB, The Netherlands. J.vanKrieken@pathol.umcn.nl
Jung
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A
Kirchner
T
T
Carneiro
F
F
Seruca
R
R
Bosman
F T
FT
Quirke
P
P
Fléjou
J F
JF
Plato Hansen
T
T
de Hertogh
G
G
Jares
P
P
Langner
C
C
Hoefler
G
G
Ligtenberg
M
M
Tiniakos
D
D
Tejpar
S
S
Bevilacqua
G
G
Ensari
A
A
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*
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