Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study
Abstract
Background The antiepidermal growth factor receptor (antiEGFR) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10% of patients with metastatic colorectal cancer that is resistant to chemotherapy. The molecular mechanisms underlying clinical response or resistance to these agents are unknown.Methods Tumours from 31 patients with metastatic colorectal cancer who had either an objective response (n=10) or stable disease or progressive disease (n=21) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors. Specifically, we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS, BRAF, and PIK3CA.Results Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation (FISH) had an increased EGFR copy number. By contrast, one of 21 non-responders assessable by FISH had an increased EGFR copy number (p<0.0001 for responders vs non-responders, Fisher's exact test). The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA, KRAS, and BRAF did not correlate with disease response. In colorectal-cancer cell lines, the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR.Interpretation We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number.
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Increased EGFR gene copy number could predict response among KRAS wild-type patients.
“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 [112]
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- Authors
- Moroni, M., Veronese, S., Benvenuti, S., Marrapese, G., Sartore-Bianchi, A., Di Nicolantonio, F., Gambacorta, M., Siena, S., & Bardelli, A.
- Affiliations
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Candiolo Cancer Institute (IT)
- IFOM (IT)
- Corresponding author
- Siena, Salvatore
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 6
- Issue
- 5
- Pages
- 279-286
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2122885616
- Cited by
- 941
- References
- 29
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 20 · 2022: 15 · 2021: 6 · 2020: 23 · 2019: 19 · 2018: 14 · 2017: 28 · 2016: 40 · 2015: 39 · 2014: 42 · 2013: 61 · 2012: 68
- FWCI
- 43.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- EGFR copy number, epidermal growth factor receptor, anti-EGFR therapy, cetuximab, panitumumab, metastatic colorectal cancer, treatment response, EGFR amplification, KRAS mutation, BRAF mutation, PIK3CA mutation, predictive biomarkers
- MeSH terms
- Cetuximab, Irinotecan, Panitumumab, Aged, Amino Acid Sequence, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Clinical Trials as Topic, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Neoplasm Metastasis, Colorectal Neoplasms, Cohort Studies, Gene Dosage, Antibodies, Monoclonal, Humanized, ErbB Receptors
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