KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer: Practical application of patient selection

Antonio Jimeno, Wells A. Messersmith, Fred R. Hirsch, Wilbur A. Franklin, S Gail Eckhardt

Research output: Contribution to journalReview article

175 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1130-1136
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number7
DOIs
StatePublished - Mar 1 2009

Fingerprint

Epidermal Growth Factor Receptor
Patient Selection
Colorectal Neoplasms
Mutation
Pharmaceutical Preparations
Patient Care
Biomarkers
Monoclonal Antibodies
Economics
Sensitivity and Specificity
Genes
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer : Practical application of patient selection. / Jimeno, Antonio; Messersmith, Wells A.; Hirsch, Fred R.; Franklin, Wilbur A.; Eckhardt, S Gail.

In: Journal of Clinical Oncology, Vol. 27, No. 7, 01.03.2009, p. 1130-1136.

Research output: Contribution to journalReview article

Jimeno, Antonio ; Messersmith, Wells A. ; Hirsch, Fred R. ; Franklin, Wilbur A. ; Eckhardt, S Gail. / KRAS mutations and sensitivity to epidermal growth factor receptor inhibitors in colorectal cancer : Practical application of patient selection. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 7. pp. 1130-1136.
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