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Updated: Jan 10, 2026

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GLMP promotes EGFR-TKI resistance by activating autophagy and RhoA pathway in non-small cell lung cancer

Xiao Liang1,2, Jiali Xu1, Suhui Shu3

  • 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

NPJ Precision Oncology
|November 26, 2025
PubMed

Insights

Glycosylated lysosomal membrane protein (GLMP) overexpression drives resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung cancer. Combined inhibition of the RhoA pathway and autophagy offers a therapeutic strategy to overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) limits treatment efficacy in lung cancer.
  • Lysosome-related mechanisms are implicated in acquired resistance to targeted therapies.

Purpose of the Study:

  • To elucidate the role of lysosome-related regulation in EGFR-TKI resistance.
  • To identify novel therapeutic targets for overcoming Osimertinib resistance in lung cancer.

Main Methods:

  • Investigated the role of glycosylated lysosomal membrane protein (GLMP) in EGFR-TKI resistance.
  • Utilized in vitro and in vivo models of Osimertinib resistance.
  • Examined the involvement of the RhoA pathway, epithelial-mesenchymal transition (EMT), and autophagy.

Main Results:

  • Overexpression of GLMP promotes Osimertinib resistance in lung cancer cells.
  • GLMP regulates RhoA ubiquitination, activating EMT and late-stage autophagy.
  • Inhibition of the RhoA pathway alone enhances early autophagy.
  • Lysosomal hyperactivity in resistant cells sustains autophagy.

Conclusions:

  • GLMP is a key mediator of EGFR-TKI resistance through lysosome-related pathways.
  • Combined inhibition of the RhoA pathway and autophagy effectively overcomes EGFR-TKI resistance.
  • This study presents a potential therapeutic strategy for enhancing EGFR-TKI efficacy in lung cancer.

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