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Mutations of the epidermal growth factor receptor gene in gastrointestinal tract tumor cell lines
Toshimoto Kimura1, Chihaya Maesawa, Kenichiro Ikeda
1Department of Pathology, Iwate Medical University School of Medicine, Uchimaru, Morioka 020-8505, Japan.
Abstract:
The epidermal growth factor receptor (EGFR) is commonly overexpressed in many human tumors including gastrointestinal tract tumors. Gefitinib is a selective inhibitor of EGFR tyrosine kinase, and blocks several signal transduction pathways including those involved in tumor cell proliferation, angiogenesis and metastasis. Recent mutational and biological studies have suggested that mutations in the tyrosine kinase domain of the EGFR gene are well correlated with the response to gefitinib, and that these mutations are frequently observed in non-small cell lung cancers affecting women, East Asians and non-smokers. This led us to speculate that EGFR gene mutations may occur frequently in gastrointestinal tract carcinomas (GITCs) because overexpression is observed in these tumor types. To investigate EGFR mutations in GICTs, we studied 11 esophageal, 6 gastric, and 12 colorectal cancer cell lines. We found a missense mutation in a gastric cancer cell line, and 10 single nucleotide polymorphisms. The occurrence of rare mutations in the tyrosine kinase domain of the EGFR gene suggests that gefitinib is unlikely to be reliable as single-drug therapy for GITCs.
Insights
Epidermal growth factor receptor (EGFR) mutations are rare in gastrointestinal tract carcinomas. This suggests gefitinib, an EGFR inhibitor, may not be effective as a standalone treatment for these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) is overexpressed in various human tumors, including gastrointestinal tract carcinomas (GITCs).
- Gefitinib, an EGFR tyrosine kinase inhibitor, targets pathways crucial for tumor growth, angiogenesis, and metastasis.
Purpose of the Study:
- To investigate the frequency of epidermal growth factor receptor (EGFR) gene mutations in gastrointestinal tract carcinomas (GITCs).
- To assess the potential efficacy of gefitinib as a single-drug therapy for GITCs based on EGFR mutation status.
Main Methods:
- Analysis of EGFR mutations in 11 esophageal, 6 gastric, and 12 colorectal cancer cell lines.
- Sequencing of the tyrosine kinase domain of the EGFR gene.
Main Results:
- A single missense mutation in the EGFR tyrosine kinase domain was identified in one gastric cancer cell line.
- Ten single nucleotide polymorphisms (SNPs) were detected across the studied cell lines.
- The overall occurrence of rare EGFR mutations in the tyrosine kinase domain was low.
Conclusions:
- The low frequency of EGFR mutations in GITCs suggests limited responsiveness to gefitinib as monotherapy.
- Further research is needed to explore alternative or combination therapies for GITCs targeting EGFR pathways.
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