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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
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The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis

Christopher J Occhiuto1,2, Jessica A Moerland1,3, Ana S Leal1,3

  • 1Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.

Molecules and Cells
|March 30, 2023
PubMed

Insights

The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway

Area of Science:

  • Cellular biology and cancer research
  • Molecular mechanisms of carcinogenesis
  • Tumor microenvironment regulation

Background:

  • The KEAP1/NRF2 pathway is crucial for cellular oxidative balance and detoxification.
  • This pathway plays a complex role in cancer development, acting as both pro- and anti-tumorigenic.
  • Understanding KEAP1/NRF2's context-dependent function is vital for cancer therapy.

Purpose of the Study:

  • To review key studies on the KEAP1/NRF2 pathway's role in different cancer stages.
  • To analyze how cancer models, tumor types, and cancer stages influence KEAP1/NRF2 activity.
  • To explore the pathway's impact on the tumor microenvironment and its modulation by epigenetics and mutations.

Main Methods:

  • Mini-review of existing scientific literature.
  • Compilation and analysis of data from key studies on the KEAP1/NRF2 pathway in cancer.
  • Focus on carcinogen-induced and genetic cancer models.

Main Results:

  • The role of KEAP1/NRF2 in cancer is highly context-dependent.
  • Factors influencing KEAP1/NRF2 activity include the experimental model, tumor type, and cancer stage.
  • KEAP1/NRF2 influences the tumor microenvironment and is affected by epigenetic modifications and co-occurring mutations.

Conclusions:

  • The KEAP1/NRF2 pathway's dual role in cancer necessitates a nuanced understanding.
  • Further research into this pathway's complexity is essential for developing targeted cancer therapies.
  • Elucidating KEAP1/NRF2 mechanisms can lead to improved pharmacological interventions and patient outcomes.
Keywords:
NRF2cancerinitiationmetastasispromotiontransformation

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