Pharmacological intervention to prevent or ameliorate chronic radiation injuries

Until the 1990s, chronic radiation-induced normal-tissue injury was viewed as being due solely to the delayed mitotic death of parenchymal or vascular cells; these injuries were held to be inevitable, progressive, and untreatable. It is now clear that parenchymal and vascular cells are active participants in the response to radiation injury rather than passive observers dying as they attempt to divide. This offers fundamentally new approaches to radiation injury because it allows for the possibility of pharmacological interventions directed at modulating steps in the cascade of events leading to expression of injury. Such interventions would be relevant to both cancer patients and victims of radiation accidents. Prophylaxis and treatment of chronic radiation injuries have been experimentally shown in multiple organ systems (eg, lung, kidney, soft tissue) and with fundamentally different pharmacological agents (eg, corticosteroids, angiotensin-converting enzyme inhibitors, pentoxifylline, superoxide dismutase). For the most part, this has been achieved using clinically relevant radiation and drug schedules and with agents that have already been approved for human use. Unfortunately, assessment of the utility of these agents for clinical use has been minimal, and there are no established mechanisms for any of the experimental or clinical successes. Clinical development of pharmacological approaches to modification of chronic radiation injuries could lead to significant improvement in survival and quality of life for radiotherapy patients and for victims of radiation accidents or nuclear terrorism.