PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer.

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.

• Authors: Hans Prenen, Jef De Schutter, Bart Jacobs, Wendy De Roock, Bart Biesmans, Bart Claes, Diether Lambrechts, Eric Van Cutsem, Sabine Tejpar
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 9 Pg. 3184-8 (May 01 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19366826 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• KRAS protein, human
• Proto-Oncogene Proteins
• Irinotecan
• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human
• ErbB Receptors
• Proto-Oncogene Proteins p21(ras)
• ras Proteins
• Cetuximab
• Camptothecin

Topics

• Adenocarcinoma (drug therapy, genetics, secondary)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Cetuximab
• Class I Phosphatidylinositol 3-Kinases
• Cohort Studies
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Drug Resistance, Neoplasm
• ErbB Receptors (antagonists & inhibitors)
• Humans
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Mutation (genetics)
• Neoplasm Staging
• Phosphatidylinositol 3-Kinases (genetics)
• Prognosis
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins p21(ras)
• Survival Rate
• Treatment Outcome
• ras Proteins (genetics)