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Targeting the Keap1/Nrf2 axis in cancer: molecular mechanisms and pharmacological interventions

Yangchen Xia1, Ziyang Xu1, Xun Yuan2

  • 1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Investigational New Drugs
|September 5, 2025
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates protective pathways but also promotes cancer. Inhibiting Nrf2 offers a potential cancer therapy strategy, especially for inflammation-related cancers.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cytoprotective mechanisms, including inflammation and redox balance.
  • Emerging evidence implicates the Nrf2 pathway in cancer development, promoting tumor cell survival and malignant transformation.
  • Nrf2's dual role necessitates a deeper understanding for targeted therapeutic interventions.

Purpose of the Study:

  • To elucidate the molecular mechanisms and biological functions of Nrf2 in cancer pathogenesis.
  • To review recent advancements in the pharmacological inhibition of Nrf2 activity for cancer therapy.
  • To discuss novel chemical compounds and clinical trial progress targeting the Nrf2 pathway.

Main Methods:

  • Literature review of molecular mechanisms regulating Nrf2.
  • Analysis of Nrf2's role in cancer biology and progression.
  • Survey of preclinical and clinical studies on Nrf2 inhibitors in cancer treatment.

Main Results:

  • Detailed description of Nrf2 regulatory networks and its pro-cancerous functions.
  • Identification of various chemical molecules designed to block Nrf2 activity.
  • Overview of the current status of Nrf2-targeted therapies in cancer trials.

Conclusions:

  • Pharmacological inhibition of Nrf2 presents a promising therapeutic avenue for cancers associated with oxidative stress and inflammation.
  • Targeting Nrf2 could disrupt cancer cell survival mechanisms and impede tumor progression.
  • Further research and clinical evaluation are crucial for optimizing Nrf2-targeted cancer therapies.
Keywords:
Antioxidant pathwayCancerKeap1Nrf2

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