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PMID: 18802721 Published · ppublish English Journal Article Review

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program.

Virchows Archiv : an international journal of pathology ·Vol. 453 ·No. 5 ·2008-11-00 ·Pages 417-31

van Krieken JH, Jung A, Kirchner T, Carneiro F, Seruca R, Bosman FT, Quirke P, Fléjou JF, Plato Hansen T, de Hertogh G, Jares P, Langner C, Hoefler G, Ligtenberg M, Tiniakos D, Tejpar S, Bevilacqua G, Ensari A

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.

MeSH Terms
Antibodies/therapeutic use Colorectal Neoplasms/drug therapy,genetics ErbB Receptors/antagonists & inhibitors,immunology Europe Genetic Testing Humans Point Mutation/genetics Predictive Value of Tests Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins p21(ras) Quality Assurance, Health Care ras Proteins/genetics
Chemicals
Antibodies KRAS protein, human Proto-Oncogene Proteins EGFR protein, human ErbB Receptors Proto-Oncogene Proteins p21(ras) ras Proteins
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
van Krieken J H J M
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500, HB, The Netherlands. [email protected]
Jung A
Kirchner T
Carneiro F
Seruca R
Bosman F T
Quirke P
Fléjou J F
Plato Hansen T
de Hertogh G
Jares P
Langner C
Hoefler G
Ligtenberg M
Tiniakos D
Tejpar S
Bevilacqua G
Ensari A
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Article Info
Journal
Virchows Archiv : an international journal of pathology
Abbr.
Virchows Arch
ISSN
0945-6317
DOI
10.1007/s00428-008-0665-y
Email
[email protected]
Published
2008-11-00
Epub
2008-00-18
Pages
417-31
Language
English
Region
Germany
NLM ID
9423843
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1007/s00428-008-0665-y View journal details
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