Radioprotection: Taking the Toll Road

Radiation therapy is a well-established and highly effective treatment for certain types of cancer, but it can destroy healthy cells in the body, especially bone marrow cells and cells in the gastrointestinal tract. Burdelya et al . have developed a drug that may prevent or reduce these side effects. The drug (a peptide called CBLB502) binds to Toll-like receptor 5 (TLR5) and activates the nuclear factor κB signaling pathway, a pathway that cancer cells often activate to avoid cell death. When mice and rhesus monkeys were treated with CBLB502 shortly before exposure to lethal doses of total body irradiation, the animals exhibited less damage to healthy bone marrow and gastrointestinal cells and survived significantly longer than controls. In tumor-bearing mice, CBLB502 did not compromise the antitumor efficacy of radiation therapy. L. G. Burdelya, V. I. Krivokrysenko, T. C. Tallant, E. Strom, A. S. Gleiberman, D. Gupta, O. V. Kurnasov, F. L. Fort, A. L. Osterman, J. A. DiDonato, E. Feinstein, A. V. Gudkov, An agonist of Toll-like receptor 5 has radioprotective activity in mouse and primate models. Science 320 , 226-230 (2008). [Abstract] [Full Text]