The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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.
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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]
Citations
Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
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High Frequency of Mutations of the PIK3CA Gene in Human Cancers
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Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer
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Somatic mutations affect key pathways in lung adenocarcinoma
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KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
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Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
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ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw235 · Cited by 3,421
Self-citationDe Roock, W., Claes, B., Bernasconi, D., De Schutter, J., Biesmans, B., Fountzilas, G., Kalogeras, K. T., Kotoula, V., Papamichael, D., Laurent-Puig, P., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70130-3 · Cited by 2,144
Self-citationBertotti, A., Migliardi, G., Galimi, F., Sassi, F., Torti, D., Isella, C., Corà, D., Di Nicolantonio, F., Buscarino, M., Petti, C., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0109 · Cited by 939
Molecular Mechanisms of Resistance to Cetuximab and Panitumumab in Colorectal Cancer
Bardelli, A., & Siena, S. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.6116 · Cited by 746
Roock, W. D., de Vriendt, V., Normanno, N., Ciardiello, F., & Tejpar, S. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70209-6 · Cited by 626
Self-citation
Metadata
- 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)
- Venue
- Clinical Cancer Research
- Published
- 2009-04-30
- Volume
- 15
- Issue
- 9
- Pages
- 3184-3188
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- 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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