PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer

Prenen, Hans; De Schutter, Jef; Jacobs, Bart; De Roock, Wendy; Biesmans, Bart; Claes, Bart; Lambrechts, Diether; Van Cutsem, Eric; Tejpar, Sabine

doi:10.1158/1078-0432.ccr-08-2961

Cited by 291Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsPI3K/AKT/mTOR signaling in cancer

PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer

Prenen, Hans, De Schutter, Jef, Jacobs, Bart, De Roock, Wendy, Biesmans, Bart, Claes, Bart, Lambrechts, Diether, Van Cutsem, Eric +1 more·2009·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-08-2961

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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.

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“Activating mutations of PIK3CA (encoding p110α) have been found in 10–20 % of CRCs [20, 68-70]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [70]

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Authors: Prenen, H., De Schutter, J., Jacobs, B., De Roock, W., Biesmans, B., Claes, B., Lambrechts, D., Van Cutsem, E., & Tejpar, S.
Affiliations: 1Department of Digestive Oncology, University Hospital Gasthuisberg,
2Center for Human Genetics K.U.Leuven, and
KU Leuven (BE)
ORCID: Prenen, Hans
Lambrechts, Diether
Tejpar, Sabine
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2009-04-30
Volume: 15
Issue: 9
Pages: 3184-3188
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-08-2961
OpenAlex: W2028035144
Cited by: 291
References: 31
Citations by year: 2025: 1 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 20 · 2015: 23 · 2014: 31 · 2013: 34 · 2012: 34
FWCI: 22.99
Type: journal article
Language: en
Open access: closed
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: PIK3CA mutation, cetuximab, EGFR inhibitors, metastatic colorectal cancer, KRAS mutation, PI3K/Akt signaling, drug resistance, irinotecan, predictive biomarkers, chemorefractory cancer
MeSH terms: Cetuximab, Irinotecan, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Prognosis, Proto-Oncogene Proteins, Colorectal Neoplasms, Cohort Studies, Survival Rate, Proto-Oncogene Proteins p21(ras), Treatment Outcome, ras Proteins, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Maximum Tolerated Dose, Class I Phosphatidylinositol 3-Kinases, Antibodies, Monoclonal, Humanized, ErbB Receptors

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PIK3CA Mutations Are Not a Major Determinant of Resistance to the Epidermal Growth Factor Receptor Inhibitor Cetuximab in Metastatic Colorectal Cancer

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