Originally published as JCO Early Release 10.1200/JCO.2008.19.8168 on January 5 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jimeno, A. Articles by Eckhardt, S. G. Search for Related Content PubMed PubMed Citation Articles by Jimeno, A. Articles by Eckhardt, S. G. Social Bookmarking                            What's this?

KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection

From the University of Colorado Cancer Center, Aurora, CO.

Corresponding author: Antonio Jimeno, MD, PhD, Medical Oncology Division, PO Box 6511, MS 8117, Aurora, CO, 80045; e-mail: Antonio.Jimeno{at}UCDenver.edu.

Recent retrospective evidence from several randomized studies has established that advanced colorectal cancer patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of epidermal growth factor receptor–directed monoclonal antibodies, such as cetuximab or panitumumab. This represents a paradigm-changing event and will have substantial impact on current and future anticancer drug development. These results add to the economic and ethical considerations involved in the development of novel targeted therapies and should increase our scrutiny of mechanisms of resistance and predictive biomarkers while in earlier developmental stages. In this article we will review the available clinical data, discuss the potential implications for future drug development in colorectal cancer, and provide a comprehensive overview of the technical aspects of KRAS mutation testing. In particular we aimed at enumerating the available procedures for mutation detection and their main characteristics, as well as comparing them from a clinical feasibility standpoint. While the true specificity and sensitivity of these methods have yet to be fully characterized, a better understanding of the differences between tests will be critical so that clinicians and pathologists can fully integrate this testing into the routine care of patients with colorectal cancer.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				V. Whitehall, K. Tran, A. Umapathy, F. Grieu, C. Hewitt, T.-J. Evans, T. Ismail, W. Q. Li, P. Collins, P. Ravetto, et al. A Multicenter Blinded Study to Evaluate KRAS Mutation Testing Methodologies in the Clinical Setting J. Mol. Diagn., November 1, 2009; 11(6): 543 - 552. [Abstract] [Full Text] [PDF]

				C. J. Allegra, J. M. Jessup, M. R. Somerfield, S. R. Hamilton, E. H. Hammond, D. F. Hayes, P. K. McAllister, R. F. Morton, and R. L. Schilsky American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy J. Clin. Oncol., April 20, 2009; 27(12): 2091 - 2096. [Abstract] [Full Text] [PDF]