PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer
- Hans Prenen1,
- Jef De Schutter2,
- Bart Jacobs2,
- Wendy De Roock2,
- Bart Biesmans2,
- Bart Claes3,
- Diether Lambrechts3,
- Eric Van Cutsem1 and
- Sabine Tejpar1,2
- Authors' Affiliations:1Department of Digestive Oncology, University Hospital Gasthuisberg, 2Center for Human Genetics K.U.Leuven, and 3The Vesalius Research Center, K.U. Leuven and VIB, Leuven, Belgium
- Requests for reprints:
Sabine Tejpar, Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Phone: 00-32-0-16-34-42-18; Fax: 00-32-0-16-34-44-19; E-mail: Sabine.Tejpar{at}uzleuven.be.
Abstract
Purpose: It has been reported that activating KRAS mutations negatively affect response to anti–epidermal growth factor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. The mutation status of signaling molecules downstream of the EGFR target is thus crucial to predict clinical benefit to EGFR-targeted therapies. Other mechanisms of resistance to EGFR inhibitors could involve activating mutations of the other main EGFR effector pathway, i.e., the PI3K/PTEN/AKT pathway.
Experimental Design: We analyzed the PIK3CA and KRAS mutation status in a large group (n = 200) of chemorefractory metastatic colorectal cancers treated with cetuximab (Erbitux) in monotherapy or in combination with irinotecan, and correlated the mutation status with outcome.
Results: Twenty-three (12%) of the 200 samples carried 1 of the PIK3CA mutations included in our assay. We found no correlation between the presence of a PIK3CA mutation and impaired response to cetuximab.
Conclusions: Our findings do not provide any evidence for a strong role of PIK3CA mutations as a single marker in determining response to cetuximab in chemorefractory metastatic colorectal cancer.
Footnotes
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Grant support: Belgian Foundation against Cancer.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: H. Prenen and J. De Schutter contributed equally to this work.
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- Accepted January 21, 2009.
- Received November 12, 2008.
- Revision received January 20, 2009.
