Molecular mechanisms and systemic targeting of NRF2 dysregulation in cancer.
Animals
Antineoplastic Agents
/ pharmacology
Gene Expression Regulation, Neoplastic
Humans
Kelch-Like ECH-Associated Protein 1
/ genetics
Lung Neoplasms
/ genetics
Molecular Targeted Therapy
Mutation
NF-E2-Related Factor 2
/ antagonists & inhibitors
Neoplasms
/ drug therapy
Quassins
/ chemistry
Tretinoin
/ pharmacology
Mutations
NF-E2-related factor 2 (NRF2)
NRF2 inhibitors
Reactive metabolites
Ubiquitination
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
02
02
2020
accepted:
24
04
2020
pubmed:
4
5
2020
medline:
15
12
2020
entrez:
4
5
2020
Statut:
ppublish
Résumé
NF-E2-related factor 2 (NRF2) is a master regulator of redox homeostasis and provides cellular protection against oxidants and electrophiles by inducing the expression of a wide array of phase II cytoprotective genes. Until now, a number of NRF2 activators have been developed for treatment of chronic diseases and some are under evaluation in the clinical studies. On the other hand, accumulating evidence indicates that NRF2 confers chemoresistance and radioresistance, and its expression is correlated with poor prognosis in cancer patients. Studies in the last decade demonstrate that diverse mechanisms such as somatic mutations, accumulation of KEAP1 binding proteins, transcriptional dysregulation, oncogene activation, and accumulation of reactive metabolites contribute to NRF2 activation in cancer. In the present review, we illustrate the molecular mechanisms governing the function of NRF2 and explain how they are hijacked in cancer. We also provide some examples of NRF2 inhibitors together with a brief explanation of their mechanisms of action.
Identifiants
pubmed: 32360363
pii: S0006-2952(20)30230-6
doi: 10.1016/j.bcp.2020.114002
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
KEAP1 protein, human
0
Kelch-Like ECH-Associated Protein 1
0
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
Quassins
0
brusatol
14907-98-3
Tretinoin
5688UTC01R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
114002Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.