Related Experiment Video

Updated: Aug 6, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

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

Tailored strategies to overcome third-generation TKI resistance in EGFR-mutated non-small cell lung cancer

Isabella Saporita1, Giovanni Farinea1, Elisa Lombardi1

  • 1Medical Oncology, Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.

Expert Opinion on Therapeutic Targets
|July 20, 2026
PubMed
Abstract

Insights

Targeting resistance mechanisms in EGFR-mutated non-small cell lung cancer (NSCLC) is key for precision medicine. Tailored therapies and molecular profiling offer improved outcomes, but optimal strategies are still evolving.

Area of Science:

  • Oncology
  • Molecular Biology
  • Precision Medicine

Background:

  • Epidermal Growth Factor Receptor (EGFR) mutations drive non-small cell lung cancer (NSCLC) treatment.
  • Resistance to EGFR-targeted therapy (EGFR-TKI) is a significant clinical challenge.
  • Understanding resistance mechanisms is crucial for optimizing NSCLC treatment.

Purpose of the Study:

  • To review resistance mechanisms to EGFR-targeted therapy in NSCLC.
  • To discuss tailored and mechanism-agnostic strategies for managing EGFR-mutated NSCLC post-progression.
  • To highlight the importance of molecular profiling in guiding treatment decisions.

Main Methods:

  • Literature review of resistance mechanisms to EGFR-targeted therapy.
  • Analysis of clinical and observational studies on tailored and mechanism-agnostic strategies.
  • Discussion of molecular assessment techniques and their role in treatment selection.

Main Results:

  • Acquired resistance involves on-target EGFR alterations, off-target pathway activation (e.g., MET amplification), and neuroendocrine transformation.
  • Combination therapies (e.g., EGFR plus MET inhibitors) show clinical activity.
  • Bispecific antibodies and antibody-drug conjugates (ADCs) are emerging options post-osimertinib.
  • Upfront combinations may alter resistance patterns and impact later-line treatment feasibility.

Conclusions:

  • Comprehensive molecular profiling via tissue and liquid biopsy is essential at progression.
  • Biomarker-driven strategies, supported by Molecular Tumor Boards, enable personalized, chemotherapy-free options.
  • Evolving resistance landscapes necessitate adaptive treatment algorithms for EGFR-mutated NSCLC.
Keywords:
EGFR mutationsHER2METNSCLCosimertinibprecision medicineresistance mechanisms

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