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Updated: Oct 4, 2025

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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Overcoming therapy resistance in EGFR-mutant lung cancer

Antonio Passaro1, Pasi A Jänne2, Tony Mok3

  • 1Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy. antonio.passaro@ieo.it.

Nature Cancer
|February 5, 2022
PubMed

Insights

Tyrosine kinase inhibitors (TKIs) offer improved outcomes for non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, acquired resistance to these treatments necessitates understanding resistance mechanisms and developing new strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Tyrosine kinase inhibitors (TKIs) have revolutionized treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.
  • Despite initial efficacy, acquired resistance to EGFR TKIs remains a significant clinical challenge, leading to disease progression.

Purpose of the Study:

  • To review the mechanisms underlying acquired resistance to EGFR TKIs in NSCLC.
  • To discuss methods for monitoring the emergence of TKI resistance.
  • To explore current and future therapeutic strategies to overcome EGFR TKI resistance.

Main Methods:

  • Literature review of studies on EGFR TKI resistance in NSCLC.
  • Analysis of molecular mechanisms driving acquired resistance.
  • Evaluation of diagnostic and monitoring techniques for resistance.
  • Synthesis of clinical data on treatment strategies.

Main Results:

  • Acquired resistance to EGFR TKIs develops through various mechanisms, including secondary mutations in EGFR and activation of bypass signaling pathways.
  • Monitoring resistance can involve liquid biopsies and advanced imaging techniques.
  • Combinatorial therapies and novel drug development show promise in overcoming resistance.

Conclusions:

  • Understanding acquired resistance mechanisms is crucial for improving long-term outcomes in EGFR-mutated NSCLC patients.
  • Integrated monitoring and strategic treatment adjustments are essential for managing TKI resistance.
  • Continued research into novel therapeutic approaches is vital to overcome acquired resistance and prolong patient survival.

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