KRAS mutation in colon cancer: A marker of resistance to EGFR-I therapy

Ahmad D. Siddiqui, Bilal Piperdi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Introduction and Design: The introduction of the epidermal growth factor receptor inhibitors (EGFR-I) has increased the treatment options available for patients with metastatic colorectal cancer (mCRC). Two EGFR-I agents currently approved for the treatment of mCRC are the fully human monoclonal antibody panitumumab and the mouse-human chimeric monoclonal antibody cetuximab. While these agents have demonstrated activity across multiple lines of therapy, early studies suggested that clinical benefit was confined to a subset of patients treated. Mutation of the KRAS oncogene has emerged as a powerful negative predictive biomarker to identify patients with mCRC who do not benefit from EGFR-I therapy. Multiple retrospective analyses have demonstrated that clinical benefit from treatment with EGFR-I is limited to patients with tumors harboring the wild-type KRAS gene. In this review, the KRAS pathway and studies evaluating KRAS as a prognostic marker in CRC are discussed along with advances in KRAS gene mutation testing. Clinical trials evaluating the role of KRAS status in response to EGFR-I monotherapy or in combination with chemotherapy are also highlighted along with ongoing studies evaluating the role of EGFR-I treatment on curative resections rates. Results and Conclusion: Future studies investigating EGFR-I therapy in mCRC should incorporate KRAS mutation testing into the study protocol in order to more accurately determine the patient population that will obtain clinical benefit from these novel agents.

Original languageEnglish (US)
Pages (from-to)1168-1176
Number of pages9
JournalAnnals of Surgical Oncology
Volume17
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Epidermal Growth Factor Receptor
Colonic Neoplasms
Mutation
Colorectal Neoplasms
Therapeutics
Monoclonal Antibodies
Combination Drug Therapy
Oncogenes
Genes
Biomarkers
Clinical Trials
Population
Neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

KRAS mutation in colon cancer : A marker of resistance to EGFR-I therapy. / Siddiqui, Ahmad D.; Piperdi, Bilal.

In: Annals of Surgical Oncology, Vol. 17, No. 4, 04.2010, p. 1168-1176.

Research output: Contribution to journalArticle

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