Related Experiment Video
Updated: Jul 2, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Impact of EGFR mutation analysis in non-small cell lung cancer
Hiromasa Yamamoto1, Shinichi Toyooka, Tetsuya Mitsudomi
1Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
Abstract:
The discovery of mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) accelerated the research of molecular-targeted therapy by EGFR-tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. About 90% of EGFR mutations are clustered in exons 19 (deletion) and 21 (point mutation at codon 858) and patients with these mutations have great response to EGFR-TKIs. However, tumors that initially respond to EGFR-TKIs almost inevitably become resistant later and T790M secondary mutation in the EGFR gene and MET amplification are reported to account for the mechanism of this acquired resistance. In this review, we summarize the recent findings about EGFR mutations, amplification, alterations of other related genes and sensitivity and acquired resistance to EGFR-TKIs. We also discuss from our studies the relationship between EGFR mutations and other molecular alterations such as aberrant methylation in tumor suppressor genes (TSGs), which indicates that they are related to the mechanism of the pathogenesis of lung cancer. The accumulated important data confer further insights on translational research, providing us with the new strategies for the treatment of NSCLCs.
Insights
EGFR mutations drive targeted therapy in non-small cell lung cancer (NSCLC). Acquired resistance mechanisms, including T790M mutations and MET amplification, necessitate new treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations in the epidermal growth factor receptor (EGFR) gene are crucial in non-small cell lung cancer (NSCLC).
- EGFR-tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib show efficacy in patients with specific EGFR mutations (exons 19 and 21).
Purpose of the Study:
- To review recent findings on EGFR mutations, amplification, and related gene alterations in NSCLC.
- To summarize acquired resistance mechanisms to EGFR-TKIs and discuss novel therapeutic strategies.
Main Methods:
- Literature review of recent studies on EGFR mutations and TKI resistance.
- Analysis of the relationship between EGFR mutations and other molecular alterations, including aberrant methylation in tumor suppressor genes.
Main Results:
- Initial response to EGFR-TKIs is often followed by acquired resistance.
- T790M secondary mutation and MET amplification are key mechanisms of acquired resistance.
- Aberrant methylation in tumor suppressor genes may be linked to EGFR mutations and lung cancer pathogenesis.
Conclusions:
- Understanding EGFR mutations and resistance mechanisms is vital for advancing NSCLC treatment.
- Further research into molecular alterations and their interplay can lead to improved therapeutic strategies for NSCLC patients.
