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

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.