Targeting antioxidant enzymes as a radiosensitizing strategy

Radiotherapy represents a major anti-cancer modality and effectively kills cancer cells through generation of reactive oxygen species (ROS). However, cancer cells are commonly characterized by increased activity of ROS-scavenging enzymes in adaptation to intrinsic oxidative stress, leading to radioresistance. Abrogation of this defense network by pharmacological ROS insults therefore is shown to improve radioresponse in preclinical models; some of them are then tested in clinical trials. In this review, we address (1) the importance of ROS in radioresponse, (2) the main systems regulating redox homeostasis with a special focus on their prognostic effect and predictive role in radiotherapy, and (3) the potential radiosensitizers acting through inhibition of antioxidant enzymes.