Study: Increased efficacy and fewer side effects may be on RT horizon

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Researchers may have uncovered a way to double the efficacy and reduce the side effects of radiation therapy, according to a study published in the December issue of International Journal of Radiation Oncology. The study detailed a method to reduce lung cancer cells' ability to repair the lethal double-strand DNA breaks caused by radiation therapy.

"Radiation is a great therapy—the problem is the side effects," William S. Dynan, PhD, associate director of research and chief, nanomedicine and gene regulation at the Georgia Health Sciences University's (GHSU) Institute of Molecular Medicine and Genetics in Augusta, said in a statement. "We think this is a way to get the same amount of cancer cell death with less radiation or use the same amount and maybe cure a patient who could not be cured before."

Radiation therapy capitalizes on radiation's ability to kill cells by causing double-strand breaks in DNA. However, all cells, including cancer cells, have internal mechanisms to prevent the lethal breakage.

GHSU scientists targeted the natural defense mechanisms by packaging a piece of an antibody against one of them with folate, which has easy access to most cells, particularly cancer cells. Many cancers, including the lung cancer cells they studied, have large numbers of folate receptors so that cancer cells get a disproportionate share of the package.

Previous efforts to destroy cancer cells' ability to avoid radiation damage have focused on receptors on their surface. To get a more direct hit, the scientists took advantage of folate receptors as a point of entry by chemically binding folate with the small piece of their antibody, ScFv 18-2. The package heads straight for the cell nucleus where a different chemical environment breaks the bond, freeing ScFv 18-2 to attack the regulatory region of DNA-dependent protein kinase, an enzyme essential to DNA repair.

"We are joining a targeting molecule with a cargo," said Dynan. "This strategy targets one of the key enzymes so it's harder to repair," the researchers said. This makes cancer cells more vulnerable to radiation.

The researchers noted the approach could be used to deliver any number of drugs directly inside cancer cells. Future studies include looking at other cell entry points as well as other targets to ensure they have the most effective package. Studies to date have been in human lung cancer cells in culture, so the next steps need to include animal studies.