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The intricacies of NRF2 regulation in cancer

Cody J Schmidlin1, Aryatara Shakya1, Matthew Dodson1

  • 1Deparment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.

Seminars in Cancer Biology
|May 21, 2021
PubMed

Insights

The transcription factor NRF2 (Nuclear factor erythroid 2-related factor 2) has a complex role in cancer. Understanding its regulation is key to developing new cancer therapies that prevent tumor initiation and progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor regulating cellular defense mechanisms.
  • NRF2 controls genes involved in redox homeostasis, DNA repair, and metabolism, crucial for cell survival under stress.
  • NRF2's role in cancer is complex, acting as both a tumor suppressor and promoter depending on context and regulation.

Purpose of the Study:

  • To explore the multifaceted regulation of NRF2 in cancer.
  • To discuss how different NRF2 activation modes influence tumor initiation, progression, and metastasis.
  • To highlight therapeutic strategies targeting NRF2 in cancer treatment.

Main Methods:

  • Review of various NRF2 regulation mechanisms: oxidative stress, autophagy dysfunction, protein-protein interactions, and epigenetics.
  • Analysis of pharmacological modulators targeting the NRF2 pathway.
  • Discussion on the impact of NRF2 induction timing and duration on cancer development.

Main Results:

  • NRF2 regulation is diverse, with activation modes dictating its role in cancer.
  • Specific NRF2 induction patterns influence tumor initiation, progression, and metastasis.
  • Development of NRF2 inhibitors shows promise for treating NRF2-addicted cancers.

Conclusions:

  • A comprehensive understanding of NRF2 regulation in specific cancer types is essential.
  • Targeting NRF2 pathways offers potential for novel cancer therapeutics.
  • Improved NRF2-targeted therapies could prevent tumor initiation, halt progression, and enhance patient survival.
Keywords:
CarcinogenesisChemopreventionChemoresistanceKEAP1NRF2

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