Radiation-Induced Cell Death: Signaling and Pharmacological Modulation

Currently, more than half of newly diagnosed cancer patients receive radiation treatment. However, the radioresistance of tumor cells as well as the early and late side effects limit the beneficial outcome of radiotherapy. Accordingly, the innovative approaches to maximize tumor killing and/or minimize radiation toxicity remain a major focus of interest. In the past decade, several pieces of evidence have shown the importance of different modes of regulated cell death (RCD) in the radioresponse of malignant and normal tissues. Furthermore, the biological modulation of radiation-induced RCDs has come to attention as a novel therapeutic means. Here, we review the major signaling pathways that orchestrate all types of RCD initiated by exposure to ionizing radiation. The latest advances in the development of small-molecule RCD modulators (both natural and synthetic) that are intended for widening the therapeutic window of radiotherapy are also discussed.