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The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications

Seyed Hossein Shahcheraghi1,2, Fateme Salemi3, Waqas Alam4

  • 1Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Medical Oncology (Northwood, London, England)
|May 14, 2022
PubMed

Insights

Glioblastoma multiforme (GBM) is a deadly brain cancer driven by abnormal signaling. Targeting the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway offers potential therapeutic strategies for GBM treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma multiforme (GBM) is an aggressive, lethal primary brain tumor.
  • GBM is characterized by rapid growth, angiogenesis, infiltration, and resistance to therapy, often due to aberrant signaling pathways.
  • The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates cellular defense mechanisms against stress.

Purpose of the Study:

  • To review the epigenetic regulation of the Nrf2/Keap1 signaling pathway in GBM.
  • To explore potential therapeutic strategies targeting Nrf2 stimulation in GBM treatment.

Main Methods:

  • Literature review focusing on epigenetic modifications impacting the Nrf2/Keap1 pathway.
  • Analysis of Nrf2's role in GBM pathogenesis and its therapeutic potential.
  • Examination of therapeutic options aimed at modulating Nrf2 activity.

Main Results:

  • Nrf2 activation, typically suppressed by Keap1 (Kelch-like ECH-associated protein 1), is crucial for adaptive cellular responses.
  • Dysregulation of the Nrf2/Keap1 pathway is implicated in GBM development and progression.
  • Epigenetic mechanisms significantly influence Nrf2/Keap1 signaling in cancer cells.

Conclusions:

  • The Nrf2/Keap1 pathway is a critical regulator of cellular protection and is frequently altered in GBM.
  • Targeting Nrf2 offers a promising therapeutic avenue for GBM, potentially overcoming treatment resistance.
  • Further research into epigenetic modulation of Nrf2 is warranted for novel GBM therapies.
Keywords:
Glioblastoma multiformeKelch-like ECH-related protein 1NF-E2-related factor 2Therapeutic options

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