UC Davis researchers discover genetic switch involved in cells' response to radiation therapy

November 16, 2005

UC Davis Cancer Center researchers have discovered a genetic switch that causes cancer cells to become more sensitive to a drug administered to enhance radiation therapy effectiveness. The switch does not make the drug more toxic.

The discovery may help scientists design new anti-cancer agents that enhance the effectiveness of radiation therapy with less toxicity than currently available radiosensitizing drugs. The finding is reported in the Priority Reports section of the last issue of the journal Cancer Research (Oct. 17 - Oct. 31).

Allan Chen, assistant professor of radiation oncology at UC Davis Cancer Center, found that Ku86, a gene involved in DNA repair, acts as a switch that, when turned off, makes cells significantly more vulnerable to the radiosensitizing property of the anti-cancer drug camptothecin.

Ku86 had no effect on the radiosensitizing abilities of other anti-cancer agents tested - etoposide, cisplatin and vinblastine. Ku86 also had no effect on camptothecin toxicity.

The team concluded that, like a switch that controls only a certain light bulb, Ku86 uniquely affects radiosensitization, but not cytotoxicity, induced by camptothecin.

The UC Davis researchers started by identifying which enzymes affect radiosensitivity and cytotoxicity, then painstakingly determined a way to control such enzymes.

The investigation focused on an enzyme called DNA topoisomerase I, which is responsible for cutting single DNA strands so that the DNA molecule can rotate and unwind during transcription and replication. Camptothecin stops DNA topoisomerase I during the unwinding process, ultimately killing the cell.
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UC Davis Cancer Center is the only National Cancer Institute-designated cancer center serving the Central Valley and inland Northern California, a region the size of Pennsylvania. Its cancer research program unites 180 scientists on three campuses, the UC Davis Medical Center campus in Sacramento, the main UC Davis campus in Davis, Calif., and the Lawrence Livermore National Laboratory in Livermore, Calif.

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