The investigation focused on Ku70, a protein involved in the early stages of DNA repair when it binds to another protein called Ku80. The work builds on their previous studies on the functional significance of Ku70 and Ku80 to radiosensitivity and the findings of Memorial Sloan-Kettering structural biologist Jonathan Goldberg, who has elucidated the structure of this vital protein complex, which works by binding to broken strands of DNA and activating crucial repair enzymes.
Some tumor cells, such as glioma cells, activate mechanisms to repair the DNA damage inflicted by radiation therapy, enabling them to survive the assault. Dr. Li and her colleagues created a mutated protein fragment called DNKu70, attached it to a virus, and placed it in glioma cells and colorectal cancer cells using gene transfer techniques. The cancer cells began producing their own DNKu70, which competed with normal Ku70 in binding to Ku80. This reduced the ability of Ku70 to participate in DNA repair when the cells were exposed to radiation. The result: tumor cells that were previously resistant to radiation fell prey to its anticancer effects.
The approach needs to be validated in animal models -- the next step the researchers are planning to take -- before evaluating it in patients.
