Related Experiment Video
Updated: May 22, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications
Clara Mayo1, Jordi Bertran-Alamillo, Miguel Ángel Molina-Vila
1Pangaea Biotech, Laboratory of Oncology, USP Dexeus University Institute, Sabino Arana, 5-19, 08028 Barcelona, Spain.
Abstract:
Lung cancer is a lethal disease, and most cases have already disseminated at the time of diagnosis. Driver mutations in the EGFR tyrosine kinase domain (mainly deletions in exon 19 and L858R mutation in exon 21) have been identified in lung adenocarcinomas, mostly in never smokers, at frequencies of 20-60%. The EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib attain a response rate of 70% and progression-free survival of 9-13 months, although there are subgroups of patients with long-lasting remissions. No significant correlation between EGFR overexpression and response to treatment has been found, while controversial results have been reported regarding EGFR gene amplification. The pretreatment presence of the T790M mutation, initially identified as an acquired resistance mutation to treatment with EGFR TKIs, has also been reported and may indicate a genetically distinct disease. Finally, other genetic factors, such as mRNA expression of BRCA1 and components of the NF-κB pathway, can modulate response to EGFR TKIs in EGFR-mutated patients.
Insights
Epidermal Growth Factor Receptor (EGFR) mutations drive lung cancer, responding to targeted therapies like gefitinib. However, other genetic factors influence treatment effectiveness in patients with EGFR-mutated lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer is a leading cause of death, often diagnosed at advanced stages.
- Specific mutations in the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase domain are common in lung adenocarcinomas, particularly in never-smokers.
- EGFR tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib show significant efficacy but with variable patient responses.
Purpose of the Study:
- To review the role of EGFR mutations in lung cancer.
- To analyze the efficacy and influencing factors of EGFR TKIs.
- To explore genetic markers that predict or modulate TKI response.
Main Methods:
- Literature review of studies on EGFR mutations and TKI treatment in lung cancer.
- Analysis of clinical data regarding response rates and progression-free survival.
- Examination of genetic factors, including EGFR overexpression, amplification, T790M mutation, BRCA1, and NF-κB pathway components.
Main Results:
- EGFR mutations (exon 19 deletions, L858R) are prevalent in lung adenocarcinomas (20-60%).
- EGFR TKIs achieve a 70% response rate and 9-13 months progression-free survival, with some patients experiencing long-term benefits.
- No clear correlation between EGFR overexpression and TKI response; EGFR gene amplification results are controversial.
- Pretreatment T790M mutation may indicate a distinct disease and impacts treatment.
- BRCA1 and NF-κB pathway gene expression can modulate TKI response in EGFR-mutated patients.
Conclusions:
- EGFR mutations are key drivers in a subset of lung cancers, making them targets for TKIs.
- Treatment response to EGFR TKIs is influenced by various genetic factors beyond the primary activating mutation.
- Further research into these genetic modulators may lead to personalized treatment strategies for lung cancer.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:29Pharmacogenomics: Identification of New Drug Targets
01:29Pharmacogenetics and Pharmacogenomics: Overview
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:27Pharmacogenetics of Drug Metabolism: Overview
02:38Mitogens and the Cell Cycle