NRF2 in human neoplasm: Cancer biology and potential therapeutic target

Pharmacol Ther. 2021 Jan:217:107664. doi: 10.1016/j.pharmthera.2020.107664. Epub 2020 Aug 15.

Abstract

Nuclear factor-erythroid 2-related factor 2 (NRF2) is a master regulator of a series of cytoprotective genes, which protects cells from stress conditions such as reactive oxygen species (ROS) and electrophiles. Besides its pivotal role in cellular physiology and stress response, several recent advances revealed that NRF2-governed pathways are extensively exploited in cancer cells, and play critical roles in granting growth advantage, supporting cancer metabolism, and promoting malignant transformation. In the present review, we focus on the regulatory mechanisms of NRF2 and its roles in cancer biology. We also discuss the value of targeting NRF2-associated pathways as a means of developing future cancer therapeutics.

Keywords: Antioxidant pathway; Cancer; Glutathione; KEAP1; NRF2; Therapy resistance.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Carcinogens / pharmacology
  • Drug Resistance, Neoplasm / physiology
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / metabolism*
  • Neoplasms / genetics
  • Neoplasms / physiopathology*
  • Oncogenes / physiology
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • beta-Transducin Repeat-Containing Proteins / metabolism

Substances

  • Carcinogens
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • beta-Transducin Repeat-Containing Proteins
  • SYVN1 protein, human
  • Ubiquitin-Protein Ligases