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Updated: Aug 26, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Minimal residual disease in EGFR-mutant non-small-cell lung cancer
Nathan T Bain1, Yang Wang1, Surein Arulananda1,2,3,4
1Department of Medical Oncology, Monash Health, Clayton, VIC, Australia.
Abstract:
Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an effective treatment for EGFR-mutant non-small-cell lung cancer (NSCLC), however most patients invariably relapse after a period of minimal residual disease (MRD). This mini-review explores the mechanistic pathways leading to tumour dormancy, cellular senescence and epigenetic changes involving YAP/TEAD activation. We describe the various approaches of utilising TKIs in combination with agents to intensify initial depth of response, enhance apoptosis and target senescence-like dormancy. This mini-review will also highlight the potential novel therapies under development targeting MRD to improve outcomes for patients with EGFR-mutant NSCLC.
Insights
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treat EGFR-mutant non-small-cell lung cancer (NSCLC) but often lead to relapse. This review explores targeting tumor dormancy and minimal residual disease (MRD) to improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted therapy with EGFR TKIs is effective for EGFR-mutant NSCLC.
- Most patients with EGFR-mutant NSCLC treated with TKIs eventually relapse due to minimal residual disease (MRD).
Purpose of the Study:
- To explore mechanisms of tumor dormancy, senescence, and epigenetic changes in EGFR-mutant NSCLC.
- To review strategies for intensifying treatment response and targeting senescence-like dormancy.
- To highlight novel therapies targeting MRD in EGFR-mutant NSCLC.
Main Methods:
- Review of mechanistic pathways including YAP/TEAD activation.
- Analysis of combination therapies involving TKIs and other agents.
- Discussion of emerging therapeutic strategies for MRD.
Main Results:
- Tumor dormancy, senescence, and epigenetic alterations contribute to TKI resistance and relapse.
- Combination therapies can enhance initial response depth and target senescence.
- Novel therapies targeting MRD show promise for improving patient outcomes.
Conclusions:
- Understanding dormancy and MRD mechanisms is crucial for overcoming TKI resistance in EGFR-mutant NSCLC.
- Targeting senescence and MRD offers new avenues for improving long-term patient survival.
- Further development of novel therapies is needed to eradicate MRD and prevent relapse.
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