The KEAP1-NRF2 pathway: Targets for therapy and role in cancer

Simone Adinolfi; Tommi Patinen; Ashik Jawahar Deen; Sini Pitkänen; Jouni Härkönen; Emilia Kansanen; Jenni Küblbeck; Anna-Liisa Levonen

doi:10.1016/j.redox.2023.102726

The KEAP1-NRF2 pathway: Targets for therapy and role in cancer

Redox Biol. 2023 Jul:63:102726. doi: 10.1016/j.redox.2023.102726. Epub 2023 Apr 29.

Authors

Simone Adinolfi¹, Tommi Patinen¹, Ashik Jawahar Deen¹, Sini Pitkänen¹, Jouni Härkönen², Emilia Kansanen³, Jenni Küblbeck¹, Anna-Liisa Levonen⁴

Affiliations

¹ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, Finland.
² A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, Finland; Department of Pathology, Hospital Nova of Central Finland, Jyväskylä, 40620, Finland.
³ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, Finland; Science Service Center, Kuopio University Hospital, Kuopio, Finland.
⁴ A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, Finland. Electronic address: anna-liisa.levonen@uef.fi.

Abstract

The KEAP1-NRF2 pathway is the key regulator of cellular defense against both extrinsic and intrinsic oxidative and electrophilic stimuli. Since its discovery in the 1990s, its seminal role in various disease pathologies has become well appreciated, motivating research to elucidate the intricacies of NRF2 signaling and its downstream effects to identify novel targets for therapy. In this graphical review, we present an updated overview of the KEAP1-NRF2 signaling, focusing on the progress made within the past ten years. Specifically, we highlight the advances made in understanding the mechanism of activation of NRF2, resulting in novel discoveries in its therapeutic targeting. Furthermore, we will summarize new findings in the rapidly expanding field of NRF2 in cancer, with important implications for its diagnostics and treatment.

Keywords: Cancer; Gene regulation; KEAP1; NRF2.

Publication types

Review

MeSH terms

Humans
Kelch-Like ECH-Associated Protein 1 / metabolism
NF-E2-Related Factor 2* / genetics
NF-E2-Related Factor 2* / metabolism
Neoplasms* / drug therapy
Neoplasms* / genetics
Oxidative Stress

Substances

NF-E2-Related Factor 2
Kelch-Like ECH-Associated Protein 1
KEAP1 protein, human