Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer

Molecules. 2021 Mar 5;26(5):1417. doi: 10.3390/molecules26051417.

Abstract

Cancer is one of the most fatal diseases with an increasing incidence and mortality all over the world. Thus, there is an urgent need for novel therapies targeting major cancer-related pathways. Nuclear factor-erythroid 2-related factor 2 (NRF2) and its major negative modulator Kelch-like ECH-associated protein 1 (KEAP1) are main players of the cellular defense mechanisms against internal and external cell stressors. However, NRF2/KEAP1 signaling pathway is dysregulated in various cancers, thus promoting tumor cell survival and metastasis. In the present review, we discuss the mechanisms of normal and deregulated NRF2 signaling pathway focusing on its cancer-related functions. We further explore activators and inhibitors of this pathway as cancer targeting drug candidates in order to provide an extensive background on the subject.

Keywords: Keap1; Nrf2; cancer; oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Epigenesis, Genetic
  • Genes, Tumor Suppressor
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / genetics
  • Kelch-Like ECH-Associated Protein 1 / metabolism*
  • Molecular Targeted Therapy / methods
  • Mutation
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oxidative Stress
  • Signal Transduction

Substances

  • KEAP1 protein, human
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Nfe2l2 protein, mouse