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Updated: Feb 19, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Immunotherapy in EGFR-TKI-resistant NSCLC: Mechanisms, therapeutic strategies, and emerging challenges

Shuyi Hu1, Xinhong Shi1, Qin Hu1

  • 1Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|February 17, 2026
PubMed

Insights

Epidermal growth factor receptor (EGFR) mutations are common in non-small cell lung cancer (NSCLC). This review covers treatment strategies for EGFR-mutated NSCLC progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Epidermal growth factor receptor (EGFR) mutations are key drivers in non-small cell lung cancer (NSCLC).
  • Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) are primary treatments for EGFR-mutated NSCLC.
  • Understanding the tumor microenvironment is crucial for treatment efficacy.

Purpose of the Study:

  • To review therapeutic options for NSCLC patients progressing after EGFR-TKI treatment.
  • To explore immunotherapy resistance mechanisms and management strategies in this population.
  • To discuss progression patterns and subsequent therapies after combined EGFR-TKI and immunotherapy treatment.

Main Methods:

  • Systematic review of current therapeutic options.
  • Overview of immunotherapy resistance mechanisms.
  • Discussion of progression patterns and subsequent therapies.

Main Results:

  • EGFR-TKIs are vital for EGFR-mutated NSCLC.
  • Resistance to EGFR-TKIs necessitates exploring alternative strategies.
  • Immunotherapy resistance mechanisms require specific management approaches.

Conclusions:

  • A treatment algorithm based on resistance, molecular profiling, and progression patterns can guide clinical decisions.
  • Effective management of EGFR-mutated NSCLC requires a comprehensive approach to sequential therapies.
  • Further research into overcoming resistance to both EGFR-TKIs and immunotherapy is warranted.
Keywords:
EGFREGFR-TKIImmuno-based therapyImmunotherapy resistanceNSCLC

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