An update of Nrf2 activators and inhibitors in cancer prevention/promotion

Abstract

Plain english summary The Nrf2 pathway signifies one of the most significant cell defense procedures against exogenous or endogenous stressors. Certainly, by increasing the expression of several cytoprotective genes, the transcription factor Nrf2 can shelter cells and tissues from multiple sources of damage including electrophilic, xenobiotic, metabolic, and oxidative stress. Notably, the aberrant activation or accumulation of Nrf2, a common event in many tumors, confers a selective advantage to cancer cells and is connected to malignant progression, therapy resistance, and poor prognosis. Therefore, lately, Nrf2 has arisen as a hopeful target in treatment of cancer, and many struggles have been made to detect therapeutic strategies intended at disrupting its pro-oncogenic role. By summarizing the outcomes from past and recent studies, this review provided an overview concerning the Nrf2 pathway and the molecular mechanisms causing Nrf2 hyperactivation in cancer cells. Finally, this paper also described some of the most promising therapeutic approaches that have been successfully employed to counteract Nrf2 activity in tumors, with a particular emphasis on the development of natural compounds and the adoption of drug repurposing strategies. Video abstract

Keywords

• Nrf2 activators
• Cancer
• Nrf2 inhibitors
• Keap1