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Updated: Jun 20, 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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The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy

Xin Jiang1, Min Yu2, Wei-Kai Wang1

  • 1Department of Medical Oncology, Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Cancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.

Acta Pharmacologica Sinica
|July 17, 2024
PubMed

Insights

Ferroptosis, a cell death process, is crucial in cancer therapy. Targeting nuclear factor E2 related factor 2 (Nrf2) alongside ferroptosis activators may overcome cancer cell resistance and improve treatment efficacy.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cancer Biology
  • Cell Death Mechanisms

Background:

  • Ferroptosis is an iron-dependent programmed cell death involving lipid peroxidation, implicated in cancer occurrence and treatment response.
  • Cancer cells develop resistance to ferroptosis by modulating oxidative stress pathways, limiting therapeutic efficacy.
  • Nuclear factor E2 related factor 2 (Nrf2) is a key transcription factor that regulates antioxidant systems and ferroptosis.

Purpose of the Study:

  • To review recent advances in Nrf2 signaling regulation and function in ferroptosis-activated cancer therapy.
  • To explore the potential of combining Nrf2 inhibitors with ferroptosis inducers for cancer treatment.

Main Methods:

  • Literature review summarizing current research on Nrf2 signaling and ferroptosis.
  • Analysis of Nrf2's role in reprogramming cellular networks related to iron, glutathione peroxidase 4 (GPX4), and antioxidant systems.
  • Exploration of therapeutic strategies targeting the Nrf2-ferroptosis axis.

Main Results:

  • Nrf2 plays a dominant role in attenuating ferroptosis by reprogramming key cellular defense networks.
  • Cancer cells' resistance to ferroptosis is linked to Nrf2-mediated adaptive responses.
  • Targeting Nrf2 signaling is crucial for enhancing ferroptosis-based cancer therapies.

Conclusions:

  • Nrf2 signaling significantly impacts ferroptosis, presenting a critical target for cancer therapy.
  • Combining Nrf2 inhibitors with ferroptosis inducers offers a promising strategy to overcome therapeutic resistance and improve cancer treatment outcomes.
Keywords:
antioxidant systemcancer therapydrug resistanceferroptosisiron metabolismnuclear factor E2 related factor 2 (Nrf2)

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