Roles of Nrf2 in drug and chemical toxicity

The transcription factor Nrf2 regulates the basal and inducible expression of numerous cell defence genes, and thus protects mammalian cells against the deleterious effects of chemical and oxidative stress. Here, we provide a concise overview of the role of Nrf2 in protection against drug and chemical toxicity, with a focus on the numerous in vivo studies that have shown heightened sensitivity of Nrf2 null (knockout) transgenic mice to such insults. In light of the emerging role for Nrf2 in driving drug resistance in cancer, we also consider the potential benefits and risks of modulating Nrf2 activity to overcome chemoresistance in patients. Finally, we highlight recent efforts to monitor perturbation of the Nrf2 pathway in vitro as part of integrated risk assessment strategies designed to identify compounds that are hazardous to human health.