Broken beyond repair. Damaging DNA in glioblastoma cells with radiation and camptothecin.

摘要

Radiosensitizers are expected to selectively enhance sensitivity of tumor cells to ionizing radiation (IR). Because cells in most solid tumors reside in a hypoxic environment, which confers radioresis-tance, one of the most common approaches to sensitize them involves oxygenation. Various drugs, however, including agents that target the DNA repair machinery, are being evaluated as potential radiosensitizers as well. Among the potential radiosensitizers are members of the DNA topoisomerase I (topi) inhibitors of the camptothecin (CPT) family, such as topotecan, irinotecan and 9-amino-CPT. These drugs, which have their own distinct antitumor activity, are also being tested regarding their capability to sensitize tumors to IR. Because these topl inhibitors are able to cross the blood-brain barrier they are particularly useful in the treatment of brain tumors. In postoperative treatment of glioblastoma multiforme (GBM), one of the most malignant brain tumors, conflicting data have been reported in terms oftheir effectiveness to sensitize tumors to IR. While some observations indicated that topi inhibitors do indeed enhance responsiveness to IR and the combined treatment yields a favorable outcome; other reports lacked such a response.