Is There a Role for IGF1R and c-MET Pathways in Resistance to Cetuximab in Metastatic Colorectal Cancer?
Abstract
Background The KRAS mutation is not responsible for all cases of resistance to anti-epidermal growth factor receptors (EGFRs) in metastatic colorectal cancer (mCRC), and new predictive and prognostic factors are actively being sought.Patients and methods We retrospectively evaluated the efficacy of a cetuximab-containing treatment in 73 patients with mCRC according to KRAS and BRAF mutational status as well as PTEN, c-MET, and insulin-like growth factor receptor (IGF1R) expression.Results Overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were significantly lower in patients with KRAS mutation than in patients with KRAS wild-type; among the population with KRAS wild-type, only 2 patients with BRAF mutations were found and neither of them achieved a response. No significant association was found between PTEN and clinical outcome. Compared with low/normal expression, c-MET overexpression significantly correlated with shorter mPFS and mOS: 3 vs. 5 months (P = .018) and 11 vs. 10 months (P = .037), respectively. In patients with high IGF1R expression, mOS was significantly longer than in those with low/normal expression (14 vs. 8 months; P = .015).Conclusion KRAS mutation significantly correlates with a worse outcome in patients treated with cetuximab, whereas no definitive inference can be drawn about the role of BRAF mutation and PTEN loss of expression. Instead, c-MET overexpression might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy. Interestingly, IGF1R overexpression seems a favorable prognostic factor in mCRC.
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Both PIK3CA exon 20 mutations and loss of PTEN expression are promising predictors of tumor suitability for anti-EGFR therapies.
“In summary, both PIK3CA exon 20 mutations and loss of PTEN expression are promising predictors of tumor suitability for anti-EGFR therapies.”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [79]
IGF-1R overexpression seems to be a favorable prognostic factor in metastatic colorectal cancer.
“IGF-1R overexpression seems to be a favorable prognostic factor [79, 106, 122]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [79]
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- Authors
- Inno, A., Di Salvatore, M., Cenci, T., Martini, M., Orlandi, A., Strippoli, A., Ferrara, A. M., Bagalà, C., Cassano, A., Larocca, L. M., & Barone, C.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Barone, Carlo
- ORCID
- Venue
- Clinical Colorectal Cancer
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 10
- Issue
- 4
- Pages
- 325-332
- ISSN
- 1533-0028 (ISSN-L)
- OpenAlex
- W2144897519
- Cited by
- 83
- References
- 46
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 19 · 2013: 12 · 2012: 9
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Colorectal Cancer (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
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- cetuximab, metastatic colorectal cancer, IGF-1 receptor, c-Met, anti-EGFR therapy resistance, KRAS mutation, BRAF mutation, PTEN loss, prognostic factors, progression-free survival, overall survival
- MeSH terms
- Cetuximab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, DNA, Neoplasm, Female, Humans, Immunoenzyme Techniques, Male, Middle Aged, Mutation, Neoplasm Metastasis, Prognosis, Proto-Oncogene Proteins, Retrospective Studies, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Survival Rate, Polymerase Chain Reaction, Proto-Oncogene Proteins p21(ras), Receptor, IGF Type 1, ras Proteins, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Proto-Oncogene Proteins B-raf, PTEN Phosphohydrolase, Antibodies, Monoclonal, Humanized, ErbB Receptors
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