PMID- 34102289
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20221102
IS  - 1096-3650 (Electronic)
IS  - 1044-579X (Print)
IS  - 1044-579X (Linking)
VI  - 76
DP  - 2021 Nov
TI  - Targeting NRF2 to treat cancer.
PG  - 61-73
LID - S1044-579X(21)00171-1 [pii]
LID - 10.1016/j.semcancer.2021.06.003 [doi]
AB  - NRF2 is a basic leucine zipper (bZip) transcription factor that is the master 
      regulator of redox homeostasis. Under basal conditions, the cellular level of 
      NRF2 is low due to a posttranslational regulation by the ubiquitin proteasome 
      system (UPS). But, when an organism is challenged with oxidative or xenobiotic 
      stress, the NRF2 pathway is activated by inhibition of the E3 ubiquitin ligase 
      complex that normally marks NRF2 for destruction. For several decades, 
      researchers have searched for molecules that can intentionally activate NRF2, as 
      this was shown to be a means to prevent certain diseases, at least in animal 
      models. In the present era, there are many compounds known to activate the NRF2 
      pathway including natural products and synthetic compounds, covalent and 
      non-covalent compounds, and others. However, it was also revealed that like many 
      protective pathways, the NRF2 pathway has a dark side. Just as NRF2 can protect 
      normal cells from damage, it can protect malignant cells from damage. As cells 
      transform, they are exposed to many stressors and aberrant upregulation of NRF2 
      can facilitate transformation and it can help cancer cells to grow, to spread, 
      and to resist treatment. For this reason, researchers are also interested in the 
      discovery and development of NRF2 inhibitors. In the present review, we will 
      begin with a general discussion of NRF2 structure and function, we will discuss 
      the latest in NRF2 non-covalent activators, and we will discuss the current state 
      of NRF2 inhibitors.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Sivinski, Jared
AU  - Sivinski J
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, University of 
      Arizona, Tucson, AZ, 85721, USA.
FAU - Zhang, Donna D
AU  - Zhang DD
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, University of 
      Arizona, Tucson, AZ, 85721, USA.
FAU - Chapman, Eli
AU  - Chapman E
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, University of 
      Arizona, Tucson, AZ, 85721, USA. Electronic address: 
      chapman@pharmacy.arizona.edu.
LA  - eng
GR  - R01 ES023758/ES/NIEHS NIH HHS/United States
GR  - P30 ES006694/ES/NIEHS NIH HHS/United States
GR  - T32 GM008804/GM/NIGMS NIH HHS/United States
GR  - R35 ES031575/ES/NIEHS NIH HHS/United States
GR  - R01 GM120350/GM/NIGMS NIH HHS/United States
GR  - R01 ES031463/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20210605
PL  - England
TA  - Semin Cancer Biol
JT  - Seminars in cancer biology
JID - 9010218
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Molecular Targeted Therapy/*methods
MH  - NF-E2-Related Factor 2/*antagonists & inhibitors
MH  - *Neoplasms
PMC - PMC8627924
MID - NIHMS1713054
OTO - NOTNLM
OT  - Cancer
OT  - Chemoprevention
OT  - NRF2
OT  - Transcription factor
COIS- Conflict of interest Eli Chapman is a cofounder of BioEL, Inc.
EDAT- 2021/06/09 06:00
MHDA- 2022/03/04 06:00
PMCR- 2022/11/01
CRDT- 2021/06/08 20:20
PHST- 2021/05/10 00:00 [received]
PHST- 2021/06/01 00:00 [revised]
PHST- 2021/06/02 00:00 [accepted]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2022/03/04 06:00 [medline]
PHST- 2021/06/08 20:20 [entrez]
PHST- 2022/11/01 00:00 [pmc-release]
AID - S1044-579X(21)00171-1 [pii]
AID - 10.1016/j.semcancer.2021.06.003 [doi]
PST - ppublish
SO  - Semin Cancer Biol. 2021 Nov;76:61-73. doi: 10.1016/j.semcancer.2021.06.003. Epub 
      2021 Jun 5.