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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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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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Methyltransferase like 7B is a potential therapeutic target for reversing EGFR-TKIs resistance in lung adenocarcinoma

Huibin Song1,2,3, Dongcheng Liu1,2, Lingwei Wang3

  • 1Department of Clinical Medical Research Center, The First Affiliated Hospital of Southern, The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, University of Science and Technology, Shenzhen, 518020, China.

Molecular Cancer
|February 11, 2022
PubMed
Abstract

Insights

Methyltransferase-like 7B (METTL7B) drives resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma by altering glutathione metabolism. Targeting METTL7B offers a promising strategy to overcome this drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Lung adenocarcinoma (LUAD) often develops resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs).
  • Identifying novel therapeutic targets is crucial for overcoming acquired resistance to EGFR-TKIs in LUAD patients.
  • Methyltransferase-like 7B (METTL7B) is investigated for its potential role in mediating EGFR-TKI resistance.

Purpose of the Study:

  • To investigate the role of METTL7B in the development of resistance to EGFR-TKIs in LUAD.
  • To determine if METTL7B can serve as a therapeutic target for reversing EGFR-TKI resistance in LUAD.

Main Methods:

  • Utilized METTL7B-overexpressed LUAD cell lines and xenograft mouse models (CDX and PDX) resistant to gefitinib and osimertinib.
  • Employed UPLC-MS/MS to identify METTL7B-regulated metabolites and MeRIP-qPCR to assess mRNA m6A modification.
  • Investigated the efficacy of gold nanocluster-assisted delivery of siRNA targeting METTL7B (GNC-siMETTL7B) in overcoming TKI resistance.

Main Results:

  • Overexpression of METTL7B induced EGFR-TKI resistance in LUAD cells both in vitro and in vivo.
  • METTL7B overexpression activated ROS metabolism, upregulating GPX4, HMOX1, and SOD1 protein levels and enzymatic activities.
  • METTL7B promoted m6A modification of GPX4, HMOX1, and SOD1 mRNA, and its knockdown re-sensitized LUAD cells to gefitinib and osimertinib.

Conclusions:

  • Established a novel link between METTL7B, glutathione metabolism, and drug resistance in LUAD.
  • METTL7B plays a critical role in mediating resistance to EGFR-TKIs by modulating ROS and glutathione metabolism.
  • METTL7B inhibitors represent a potential therapeutic strategy for reversing TKI resistance in LUAD patients.
Keywords:
Glutathione metabolismLung adenocarcinomasMETTL7BTKIs resistancem6A modification

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