radioprotectors

Radioprotectors are substances that reduce the harmful effects of ionizing radiation on normal tissues. They are used in clinical radiotherapy to spare healthy tissue, in contexts of accidental or intentional radiation exposure, and in spaceflight research to limit radiation injury. The goal is to maximize tumor control while minimizing damage to normal cells.

Most radioprotectors act by limiting DNA damage or its consequences. The primary mechanism is scavenging of free radicals produced by radiation, thereby reducing initial injury. Some agents also modulate DNA repair processes, dampen inflammatory responses, or bolster cellular antioxidant defenses. A major challenge is that many compounds can also protect tumor cells, potentially diminishing treatment efficacy, so selective protection of normal tissues is a key consideration.

The best-known radioprotector in clinical use is amifostine (WR-2721), a prodrug converted to the active thiol WR-1065 in normal tissues. It scavenges free radicals and provides cytoprotection, and is approved to reduce xerostomia in head-and-neck cancer patients and to lessen cisplatin nephrotoxicity. It is given by intravenous or subcutaneous administration and can cause hypotension, nausea, vomiting, and hypersensitivity reactions; it is contraindicated in certain cardiovascular or renal conditions. Palifermin, a keratinocyte growth factor, is approved to reduce severe oral mucositis in patients undergoing stem cell transplantation, representing a tissue-specific protective approach rather than a broad radioprotector.

Beyond amifostine and palifermin, research explores various antioxidants, sulfhydryl donors, cytokines, and other agents. No universal radioprotector exists, and safety concerns include potential tumor protection and adverse systemic effects, guiding careful, context-specific use.