Repurposing Drugs for Cancer Radiotherapy: Early Successes and Emerging Opportunities

It has long been recognized that combining radiotherapy with cytotoxic drugs such as cisplatin can improve efficacy. However, while concurrent chemoradiotherapy improves patient outcomes, it comes at costs of increased toxicity. A tremendous opportunity remains to investigate drug combinations in the clinical setting that might increase the benefits of radiation without additional toxicity. This chapter highlights opportunities to apply repurposing of drugs along with a mechanistic understanding of radiation effects on cancer and normal tissue to discover new therapy-modifying drugs and help rapidly translate them to the clinic. We survey candidate radiosensitizers that alter DNA repair, decrease hypoxia, block tumor survival signaling, modify tumor metabolism, block growth factor signaling, slow tumor invasiveness, impair angiogenesis, or stimulate antitumor immunity. Promising agents include widely used drugs such as aspirin, metformin, and statins, offering the potential to improve outcomes, decrease radiation doses, and lower costs. Many other candidate drugs are also discussed.