The Dual Roles of NRF2 in Cancer.
NRF2 has been traditionally considered as a tumor suppressor because its cytoprotective functions are deemed to be the main cellular defense mechanism against exogenous and endogenous insults, including xenobiotics and oxidative stress. However, several recent studies demonstrate that hyperactivation of the NRF2 pathway creates an environment that favors the survival of normal as well as malignant cells, protecting them against oxidative stress, chemotherapeutic agents, and radiotherapy. In a rapidly advancing field, this review summarizes some of the known mechanisms by which NRF2 can exert its oncogenic functions, and describes the current status of NRF2 inhibitors, providing a clear rationale for the consideration of NRF2 as a powerful putative therapeutic target in cancer treatment.
University of Torino, Department of Oncology, Candiolo Cancer Institute-FPO, IRCCS, Strada Provinciale 142, 10060 Candiolo, Torino, Italy. Electronic address: silvia.menegon@ircc.it.
Silvia
S
Menegon
Department of Biomedical Sciences, University of Cagliari, Via Porcell 4, 09124 Cagliari, Italy. Electronic address: columbano@unica.it.
Amedeo
A
Columbano
University of Torino, Department of Oncology, Candiolo Cancer Institute-FPO, IRCCS, Strada Provinciale 142, 10060 Candiolo, Torino, Italy. Electronic address: silvia.giordano@unito.it.
Silvia
S
Giordano
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D000072019:Kelch-Like ECH-Associated Protein 1; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human
KEAP1; NRF2; antioxidant response; mutations