The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer
Abstract
Purpose: The occurrence of KRAS mutation is predictive of nonresponse and shorter survival in patients treated by anti–epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors. However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy. Patients and Methods: We retrospectively collected tumors from 173 patients with mCRC. All but one patient received a cetuximab-based regimen as second-line or greater therapy. KRAS and BRAF status were assessed by allelic discrimination. EGFR amplification was assessed by chromogenic in situ hybridization and fluorescent in situ hybridization, and the expression of PTEN was assessed by immunochemistry. Results: In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = .063) but were strongly associated with shorter progression-free survival (P < .001) and shorter overall survival (OS; P < .001). A high EGFR polysomy or an EGFR amplification was found in 17.7% of the patients and was associated with response (P = .015). PTEN null expression was found in 19.9% of the patients and was associated with shorter OS (P = .013). In multivariate analysis, BRAF mutation and PTEN expression status were associated with OS. Conclusion: BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.
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In the citing paper
“Although therapies targeting EGFR have some efficacy in CRCs without KRAS mutations (1, 5–8)”
From mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1 (2014) · cites this paper as [6]
In the citing paper
“and also of low RRs to cetuximab and panitumumab [18, 20, 52, 53].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [53]
In the citing paper
“The BRAF V600E mutation has been described as a predictor of tumor aggressiveness in metastatic disease [33, 52, 53]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [53]
In the citing paper
“Increased EGFR gene copy number could predict response among KRAS wild-type patients [53, 91, 111-113]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [53]
In the citing paper
“PTEN is a negative regulator in the PI3K/AKT pathway and was found in 20–40% of mCRC [106, 107].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [107]
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Metadata
- Authors
- Laurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., Ducreux, M., Ychou, M., Bibeau, F., Bouché, O., Reid, J., Stone, S., & Penault-Llorca, F.
- Affiliations
- From the Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) -S775 Molecular Basis of Xenobiotics Response; Université Paris Descartes; Assistance Publique–Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hôpital Ambroise Paré, Paris; Centre Jean Perrin, Université d'Auvergne Equipe Associée EA4233 Centre Hospitalier Universitaire (CHU), Clermont-Ferrand; CHU, Tours; Institut Gustave Roussy, Villejuif; Centre Régional de Lutte contre le Cancer (CRLC) Val...
- Inserm (FR)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2009-12-10
- Volume
- 27
- Issue
- 35
- Pages
- 5924-5930
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2125229905
- Cited by
- 673
- References
- 39
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 16 · 2023: 6 · 2022: 10 · 2021: 22 · 2020: 16 · 2019: 27 · 2018: 26 · 2017: 32 · 2016: 45 · 2015: 55 · 2014: 81 · 2013: 73 · 2012: 85
- FWCI
- 41.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- cetuximab, metastatic colorectal cancer, KRAS wild-type, BRAF mutation, PTEN expression, EGFR amplification, predictive biomarkers, anti-EGFR antibody therapy, progression-free survival, overall survival, treatment response
- MeSH terms
- Cetuximab, Antibodies, Monoclonal, Antineoplastic Agents, France, Gene Amplification, Humans, Immunohistochemistry, Mutation, Predictive Value of Tests, Proto-Oncogene Proteins, Retrospective Studies, Time Factors, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), Treatment Outcome, In Situ Hybridization, In Situ Hybridization, Fluorescence, Risk Assessment, Disease-Free Survival, Patient Selection, ras Proteins, Proto-Oncogene Proteins B-raf, PTEN Phosphohydrolase, Kaplan-Meier Estimate, Precision Medicine, Antibodies, Monoclonal, Humanized, ErbB Receptors
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