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Updated: Jun 1, 2025

Translational Orthotopic Models of Glioblastoma Multiforme
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Translational Orthotopic Models of Glioblastoma Multiforme

Published on: February 17, 2023

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It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma

Rebeca Yakubov1,2, Ramneet Kaloti1,2, Phooja Persaud1,2

  • 1MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.

Journal of Neuro-Oncology
|January 17, 2025
PubMed
Abstract

Insights

Targeting transcription factors offers a novel strategy to overcome resistance in glioblastoma (GBM) treatment. Inhibiting the receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK pathway can be combined with transcription factor therapies for improved GBM outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • The receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK pathway is frequently hyperactivated in glioblastoma (GBM), driving aggressive tumor behavior.
  • Despite targeted therapies, clinical success is limited by acquired resistance mechanisms within this pathway.

Purpose of the Study:

  • To review how RTK/Ras/Raf/MEK/ERK pathway inhibition impacts transcription factors.
  • To explore the contribution of transcription factor dysregulation to acquired resistance in GBM.
  • To highlight the role of transcription factor alterations in therapeutic resistance.

Main Methods:

  • Synthesis of findings from key studies on the RTK/Ras/Raf/MEK/ERK pathway in GBM.
  • Exploration of transcription factor dysregulation in response to targeted therapies, radiation, and chemotherapy.

Main Results:

  • Inhibition of the RTK/Ras/Raf/MEK/ERK pathway leads to significant transcription factor dysregulation.
  • This dysregulation is a key mechanism contributing to therapeutic resistance in GBM.

Conclusions:

  • Transcription factors represent promising therapeutic targets for overcoming GBM treatment resistance.
  • Combination strategies involving RTK/Ras/Raf/MEK/ERK pathway inhibitors and transcription factor-targeted therapies offer a novel approach.
  • Continued research and advancements in precision medicine are crucial for refining these strategies and improving patient outcomes.
Keywords:
GlioblastomaRTK/Raf/MEK/ERK inhibitorsResistance mechanismsTranscription factors

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