Gene therapy may protect normal tissues during radiation retreatment for lung cancer

Gene therapy could be used as an agent to protect normal tissues, including the esophagus and lung, from damage during a second administration of radiation therapy for non-small cell lung cancer, according to an animal study presented today by University of Pittsburgh researchers at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Denver.

“A major challenge in treating lung tumors with radiation is the toxicity of radiation to healthy tissue,” said Joel S. Greenberger, M.D., professor, University of Pittsburgh School of Medicine. “This can result in major quality-of-life issues for lung cancer patients receiving radiation therapy for their diseases. In previous studies, we demonstrated that gene therapy may protect healthy tissues from damage prior to an initial course of radiation therapy. In this study, we found that gene therapy also can protect the same healthy tissue during retreatment with radiation.” Dr. Greenberger explained that a related study shows the effectiveness of aerosol delivery of this therapy by an inhalation nebulizer making it clinically feasible.

In the study, animal models were used to test the protective effects of manganese superoxide dismutase plasmid liposome (MnSOD-PL) gene therapy during exposure to radiation. One group of mice received an intratracheal injection of MnSOD-PL 24 hours before a course of 14 Gy irradiation, while a second group received 14 Gy irradiation alone. The mice were observed for six months for any toxic pulmonary effects and then subdivided into two more groups. One of these groups was exposed to a second lung irradiation of 10 Gy without MnSOD-PL and the other received an injection of MnSOD-PL 24 hours prior to radiation exposure.

The researchers found that in mice that received the initial 14 Gy dose there was 50 percent survival at 180 days (due to lung toxicity) compared to 87.5 percent survival during the same length of time for mice that were injected with MnSOD-PL prior to irradiation. Mice that received MnSOD-PL before both the 14 Gy dose as well as the subsequent 10 Gy dose had the best survival rate overall. Mice treated with MnSOD-PL before the first dose of radiation had a survival rate of 31.6 percent, while mice receiving the treatment before both courses of radiation had a survival rate of 47.6 percent.

“Administration of this type of gene therapy appeared to prevent the damaging effects of radiation, even when the radiation was re-administered after six months,” said Dr. Greenberger. “Future studies will tell us whether this therapy can improve the quality of life for lung cancer patients and help us more effectively treat lung cancer without the damaging side effects.”

Lung cancer is the leading cause of cancer-related death in men and women. In 2005, more than 170,000 new cases of lung cancer will be diagnosed. Side effects from radiation therapy for lung cancer can include fatigue, skin changes, swelling of the esophagus, hair loss in the treated area, dry cough caused by swelling of the lung tissue and sore throat.