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FGFR1 Induces Acquired Resistance Against Gefitinib By Activating AKT/mTOR Pathway In NSCLC

Dan Zhang1,2, Li-Li Han3, Fen Du4

  • 1College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, Henan, People's Republic of China.

Oncotargets and Therapy
|December 11, 2019
PubMed
Abstract

Insights

Fibroblast growth factor receptor 1 (FGFR1) drives gefitinib resistance in non-small-cell lung cancer (NSCLC) by activating the AKT/mTOR pathway. FGFR1 presents a potential therapeutic target for overcoming gefitinib resistance in NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) effective against EGFR-mutant non-small-cell lung cancer (NSCLC).
  • Acquired resistance to gefitinib is a significant clinical challenge in NSCLC treatment.
  • The precise mechanisms underlying gefitinib resistance remain incompletely understood.

Purpose of the Study:

  • To investigate the role of fibroblast growth factor receptor 1 (FGFR1) in mediating gefitinib resistance in NSCLC.
  • To elucidate the molecular mechanisms by which FGFR1 contributes to gefitinib resistance.

Main Methods:

  • High-throughput sequencing to compare mRNA expression profiles of gefitinib-sensitive and resistant NSCLC cells.
  • Immunohistochemistry and Kaplan-Meier survival analysis to assess the clinical significance of FGFR1 in NSCLC.
  • In vitro assays including confocal microscopy, Western blotting, transwell, colony formation, CCK-8, and apoptosis assays to analyze molecular mechanisms.

Main Results:

  • FGFR1 is highly expressed in NSCLC tissues and correlates with poor prognosis.
  • FGFR1 promotes proliferation and migration of gefitinib-resistant NSCLC cells and mediates resistance.
  • FGFR1 activates the AKT/mTOR signaling pathway, which is crucial for acquired gefitinib resistance.

Conclusions:

  • FGFR1 plays a critical role in acquired gefitinib resistance in NSCLC.
  • The FGFR1/AKT/mTOR signaling pathway is implicated in gefitinib resistance.
  • FGFR1 represents a potential novel biomarker and therapeutic target for overcoming gefitinib resistance in NSCLC.
Keywords:
AKT/mTOR pathwayFGFR1NSCLCacquired resistancefibroblast growth factor receptor 1gefitinibnon-small-cell lung cancer

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