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Updated: Jul 12, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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NRF2 connects Src tyrosine kinase to ferroptosis resistance in glioblastoma

Claudia Cirotti1,2, Irene Taddei3,2, Claudia Contadini3,2,4

  • 1Department of Biology, University of Rome "Tor Vergata," Rome, Italy claudiacirotti89@gmail.com.

Life Science Alliance
|October 25, 2023
PubMed

Insights

Src tyrosine kinase activation promotes glioblastoma resistance to radiation therapy by inhibiting ferroptosis. Targeting the Src-NRF2 pathway could enhance treatment effectiveness for this aggressive brain tumor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma is an aggressive brain tumor with poor patient survival rates.
  • Cancer cells resist standard therapies like radiation and temozolomide by altering signaling pathways.
  • Upregulation of ferroptosis inhibitors is linked to cancer resistance to ionizing radiation, but the molecular link to oncogenic signaling is unclear.

Purpose of the Study:

  • To elucidate the molecular connection between activated tyrosine kinases and ferroptosis resistance in glioblastoma.
  • To investigate the role of Src tyrosine kinase in regulating ferroptosis and radiation resistance.
  • To identify potential therapeutic targets for overcoming glioblastoma treatment resistance.

Main Methods:

  • Investigated the role of Src tyrosine kinase in glioblastoma cell signaling.
  • Analyzed the impact of Src activation on ferroptosis pathways.
  • Assessed the effect of targeting the Src-NRF2 axis on glioblastoma response to ionizing radiation.

Main Results:

  • Demonstrated a molecular link between constitutive tyrosine kinase activation and ferroptosis resistance.
  • Showed that Src tyrosine kinase stabilizes and activates the NRF2 pathway.
  • Established that the Src-NRF2 axis promotes resistance to ionizing radiation-induced ferroptosis in glioblastoma.

Conclusions:

  • The Src-NRF2 axis is a key mediator of ferroptosis resistance in glioblastoma.
  • Targeting the Src-NRF2 pathway represents a potential strategy to enhance glioblastoma sensitivity to radiation therapy.
  • Inhibition of ferroptosis resistance may improve outcomes for glioblastoma patients.

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