Related Experiment Video

Updated: Oct 11, 2025

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

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Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in

N Coleman1, L Hong2, J Zhang2

  • 1Department of Investigational Cancer Therapeutics (Phase I Program), University of Texas MD Anderson Cancer Center, Houston, USA.

ESMO Open
|November 27, 2021
PubMed

Insights

MET amplification drives resistance in lung cancer treated with targeted therapies. Combining MET and EGFR inhibitors shows promise in overcoming this resistance, with ongoing trials exploring this strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The treatment landscape for metastatic oncogene-driven non-small-cell lung cancer (NSCLC) is rapidly evolving.
  • Understanding resistance mechanisms is crucial for advancing patient care.

Purpose of the Study:

  • To review MET amplification as a key driver of acquired resistance in various molecular subsets of NSCLC.
  • To explore the biological mechanisms underlying MET amplification-mediated resistance.
  • To summarize recent clinical data and combination strategies for overcoming MET amplification resistance.

Main Methods:

  • Literature review of published clinical trials and biological studies.
  • Analysis of resistance profiling data in EGFR-mutant, ALK-, RET-, and ROS-1-fusion NSCLC.
  • Synthesis of emerging data on combination therapies targeting MET and other oncogenic drivers.

Main Results:

  • MET amplification is a frequent resistance mechanism in EGFR-mutant NSCLC.
  • MET amplification also drives resistance in ALK-, RET-, and ROS-1-fusion NSCLC (approx. 15%).
  • Combination therapies targeting MET and EGFR TKIs demonstrate clinical promise in overcoming resistance.

Conclusions:

  • MET amplification is a significant, targetable mechanism of acquired resistance across multiple oncogene-driven NSCLC subtypes.
  • Combination strategies involving MET and EGFR tyrosine kinase inhibitors (TKIs) are effective in overcoming MET amplification-dependent resistance.
  • Further clinical trials are investigating these combination approaches to improve outcomes for NSCLC patients.
Keywords:
EGFRMETNSCLCamplificationresistancetargeted therapy

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