Gene Therapy May Protect Normal Tissues During Radiation Retreatment For Lung Cancer

"A major challenge in treating lung tumors with radiation is thetoxicity of radiation to healthy tissue," said Joel S. Greenberger,M.D., professor, University of Pittsburgh School of Medicine. "This canresult in major quality-of-life issues for lung cancer patientsreceiving radiation therapy for their diseases. In previous studies, wedemonstrated that gene therapy may protect healthy tissues from damageprior to an initial course of radiation therapy. In this study, wefound that gene therapy also can protect the same healthy tissue duringretreatment with radiation." Dr. Greenberger explained that a relatedstudy shows the effectiveness of aerosol delivery of this therapy by aninhalation nebulizer making it clinically feasible.

In the study, animal models were used to test the protective effects ofmanganese superoxide dismutase plasmid liposome (MnSOD-PL) gene therapyduring exposure to radiation. One group of mice received anintratracheal injection of MnSOD-PL 24 hours before a course of 14 Gyirradiation, while a second group received 14 Gy irradiation alone. Themice were observed for six months for any toxic pulmonary effects andthen subdivided into two more groups. One of these groups was exposedto a second lung irradiation of 10 Gy without MnSOD-PL and the otherreceived an injection of MnSOD-PL 24 hours prior to radiation exposure.

The researchers found that in mice that received the initial 14Gy dose there was 50 percent survival at 180 days (due to lungtoxicity) compared to 87.5 percent survival during the same length oftime 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 thesubsequent 10 Gy dose had the best survival rate overall. Mice treatedwith MnSOD-PL before the first dose of radiation had a survival rate of31.6 percent, while mice receiving the treatment before both courses ofradiation had a survival rate of 47.6 percent.

"Administration of this type of gene therapy appeared to prevent thedamaging effects of radiation, even when the radiation wasre-administered after six months," said Dr. Greenberger. "Futurestudies will tell us whether this therapy can improve the quality oflife for lung cancer patients and help us more effectively treat lungcancer without the damaging side effects."

Lung cancer is the leading cause of cancer-related death in men andwomen. In 2005, more than 170,000 new cases of lung cancer will bediagnosed. Side effects from radiation therapy for lung cancer caninclude fatigue, skin changes, swelling of the esophagus, hair loss inthe treated area, dry cough caused by swelling of the lung tissue andsore throat.

The study's co-authors include Lauren Hricisak and Michael W. Epperly,Ph.D., both with the department of radiation oncology at the Universityof Pittsburgh. The study was one of several funded by a SpecializedProgram in Research Excellence in Lung Cancer awarded to the Universityof Pittsburgh Cancer Institute by the National Cancer Institute in 2001.