NRF2 and cancer: the good, the bad and the importance of context.
Many studies of chemopreventive drugs have suggested that their beneficial effects on suppression of carcinogenesis and many other chronic diseases are mediated through activation of the transcription factor NFE2-related factor 2 (NRF2). More recently, genetic analyses of human tumours have indicated that NRF2 may conversely be oncogenic and cause resistance to chemotherapy. It is therefore controversial whether the activation, or alternatively the inhibition, of NRF2 is a useful strategy for the prevention or treatment of cancer. This Opinion article aims to rationalize these conflicting perspectives by critiquing the context dependence of NRF2 functions and the experimental methods behind these conflicting data.
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. e-michael.sporn@dartmouth.edu
Michael B
MB
Sporn
Karen T
KT
Liby
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D016588:Anticarcinogenic Agents; D051267:NF-E2-Related Factor 2; D025521:Tumor Suppressor Proteins