Targeting the Keap1/Nrf2 axis in cancer: molecular mechanisms and pharmacological interventions.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is the first-line regulator of a plethora of cytoprotective pathways, such as inflammation, redox metabolism, and proteostasis. Besides its protective role in oxidative stress, several recent advances suggested that the Nrf2 pathway is extensively involved in cancer pathogenesis and confers a survival advantage and malignant transformation. Therefore, pharmacological inhibition of Nrf2 is a potential therapeutic approach for cancer that is related to oxidative stress and inflammation. In this review, we first describe the molecular regulatory mechanisms of Nrf2 and its biological function in cancer. Then, we discuss the recent progress of blocking Nrf2 activity, comprising novel chemical molecules, and the advance in preclinical or clinical trials in cancer therapy.