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The emerging role of the Nrf2-Keap1 signaling pathway in cancer

Melba C Jaramillo1, Donna D Zhang

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85721, USA;

Genes & Development
|October 22, 2013
PubMed

Insights

The Nrf2-Keap1 pathway protects cells but also cancer cells, promoting chemoresistance and poor prognosis. Understanding this dual role is key for developing new cancer therapies.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • The Nrf2-Keap1 signaling pathway is crucial for cellular defense against toxicants.
  • Nrf2 activation increases cytoprotective gene expression, making it a target for chemoprevention.
  • Aberrant Nrf2 accumulation in cancer is linked to poor prognosis and drug resistance.

Purpose of the Study:

  • To review the Nrf2-Keap1 signaling pathway.
  • To elucidate the dual role of Nrf2 in cancer, including its protective and detrimental effects.
  • To discuss the molecular mechanisms of Nrf2 activation in cancer and challenges in therapeutic development.

Main Methods:

  • Literature review of Nrf2-Keap1 pathway.
  • Analysis of Nrf2's role in cancer cell protection and progression.
  • Examination of molecular basis for Nrf2 activation in cancer.
  • Discussion of challenges in Nrf2-targeted drug development.

Main Results:

  • Nrf2 protects normal cells from toxicants but also protects cancer cells from chemotherapy.
  • Nrf2 accumulation in cancer correlates with poor patient prognosis.
  • Nrf2 activation contributes to both intrinsic and acquired chemoresistance.

Conclusions:

  • Nrf2 plays a dual role in cancer, acting as both a tumor suppressor and a promoter.
  • Targeting Nrf2 presents challenges due to its complex role in chemoresistance.
  • Further research is needed to develop effective Nrf2-based strategies for cancer chemoprevention and chemotherapy.
Keywords:
AREKeap1Nrf2chemopreventionchemoresistanceoxidative stress

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