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Molecular mechanisms and systemic targeting of NRF2 dysregulation in cancer

Jong-Su Kang1, Le Ba Nam1, Ok-Kyung Yoo1

  • 1College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, 32 Dongguk-ro, Goyang, Gyeonggi-do 10326, Republic of Korea.

Biochemical Pharmacology
|May 4, 2020
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cellular defense but promotes cancer resistance. This review details NRF2

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of cellular defense against oxidative stress.
  • NRF2 activators are explored for chronic diseases, but NRF2 also promotes cancer chemoresistance and radioresistance.
  • Elevated NRF2 expression correlates with poor prognosis in cancer patients.

Purpose of the Study:

  • To review the molecular mechanisms of NRF2 function.
  • To explain how NRF2 is dysregulated in cancer.
  • To present examples of NRF2 inhibitors and their mechanisms.

Main Methods:

  • Literature review of NRF2 function and dysregulation in cancer.
  • Analysis of molecular mechanisms underlying NRF2 activation in cancer.
  • Compilation of data on NRF2 inhibitors.

Main Results:

  • NRF2 activation in cancer involves diverse mechanisms including somatic mutations and oncogene activation.
  • NRF2 confers resistance to chemotherapy and radiotherapy.
  • Several NRF2 inhibitors are being developed.

Conclusions:

  • Understanding NRF2's dual role is crucial for cancer therapy.
  • Targeting NRF2 may offer new strategies to overcome cancer resistance.
  • Further research into NRF2 inhibitors is warranted.
Keywords:
MutationsNF-E2-related factor 2 (NRF2)NRF2 inhibitorsReactive metabolitesUbiquitination

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