Development of targeted therapy of NRF2high esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease and one of the most aggressive cancers of the gastrointestinal tract. As a master transcription factor regulating the stress response, NRF2 is often mutated and becomes hyperactive, and thus causes chemo-radioresistance and poor survival in human ESCC. There is a great need to develop NRF2 inhibitors for targeted therapy of NRF2high ESCC. In this review, we mainly focus on three aspects, NRF2 inhibitors and their mechanisms of action, screening novel drug targets, and evaluation of NRF2 activity in the esophagus. A research strategy has been proposed to develop NRF2 inhibitors using human ESCC cells and mouse models.