PMID- 32106613
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 9
IP  - 3
DP  - 2020 Feb 25
TI  - Potential Applications of NRF2 Modulators in Cancer Therapy.
LID - 10.3390/antiox9030193 [doi]
LID - 193
AB  - The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated 
      protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells 
      and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling 
      the transactivation of over 500 cytoprotective genes, the NRF2 transcription 
      factor has been implicated in the physiopathology of several human diseases, 
      including cancer. In this respect, accumulating evidence indicates that NRF2 can 
      act as a double-edged sword, being able to mediate tumor suppressive or 
      pro-oncogenic functions, depending on the specific biological context of its 
      activation. Thus, a better understanding of the mechanisms that control NRF2 
      functions and the most appropriate context of its activation is a prerequisite 
      for the development of effective therapeutic strategies based on NRF2 modulation. 
      In line of principle, the controlled activation of NRF2 might reduce the risk of 
      cancer initiation and development in normal cells by scavenging reactive-oxygen 
      species (ROS) and by preventing genomic instability through decreased DNA damage. 
      In contrast however, already transformed cells with constitutive or prolonged 
      activation of NRF2 signaling might represent a major clinical hurdle and exhibit 
      an aggressive phenotype characterized by therapy resistance and unfavorable 
      prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on 
      the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, 
      describing the mechanisms of its activation and potential therapeutic strategies 
      based on the use of context-specific modulation of NRF2.
FAU - Panieri, Emiliano
AU  - Panieri E
AD  - Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza 
      University of Rome, 00185 Rome, Italy.
FAU - Buha, Aleksandra
AU  - Buha A
AD  - Department of Toxicology "Akademik Danilo Soldatovic", University of 
      Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia.
FAU - Telkoparan-Akillilar, Pelin
AU  - Telkoparan-Akillilar P
AD  - Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, 
      06520 Balgat, Ankara, Turkey.
FAU - Cevik, Dilek
AU  - Cevik D
AD  - Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, 
      06520 Balgat, Ankara, Turkey.
FAU - Kouretas, Demetrios
AU  - Kouretas D
AD  - Department of Biochemistry-Biotechnology University of Thessaly Viopolis, 
      Mezourlo, 41500 Larissa, Greece.
FAU - Veskoukis, Aristidis
AU  - Veskoukis A
AD  - Department of Biochemistry-Biotechnology University of Thessaly Viopolis, 
      Mezourlo, 41500 Larissa, Greece.
FAU - Skaperda, Zoi
AU  - Skaperda Z
AD  - Department of Biochemistry-Biotechnology University of Thessaly Viopolis, 
      Mezourlo, 41500 Larissa, Greece.
FAU - Tsatsakis, Aristidis
AU  - Tsatsakis A
AD  - Laboratory of Toxicology Science and Research, Medical School, University of 
      Crete, 71003 Heraklion, Crete, Greece.
FAU - Wallace, David
AU  - Wallace D
AD  - School of Biomedical Science, Oklahoma State University Center for Health 
      Sciences, Tulsa, OK 74107-1898, USA.
FAU - Suzen, Sibel
AU  - Suzen S
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 
      06100 Tandogan, Ankara, Turkey.
FAU - Saso, Luciano
AU  - Saso L
AD  - Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza 
      University of Rome, 00185 Rome, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200225
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC7139512
OTO - NOTNLM
OT  - NRF2-KEAP1
OT  - ROS
OT  - antioxidant
OT  - cancer metabolism
OT  - cancer therapy
OT  - chemoresistance
OT  - oxidative stress
OT  - radioresistance
COIS- The authors declare no conflicts of interest.
EDAT- 2020/02/29 06:00
MHDA- 2020/02/29 06:01
PMCR- 2020/02/25
CRDT- 2020/02/29 06:00
PHST- 2020/01/30 00:00 [received]
PHST- 2020/02/21 00:00 [revised]
PHST- 2020/02/21 00:00 [accepted]
PHST- 2020/02/29 06:00 [entrez]
PHST- 2020/02/29 06:00 [pubmed]
PHST- 2020/02/29 06:01 [medline]
PHST- 2020/02/25 00:00 [pmc-release]
AID - antiox9030193 [pii]
AID - antioxidants-09-00193 [pii]
AID - 10.3390/antiox9030193 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2020 Feb 25;9(3):193. doi: 10.3390/antiox9030193.