Blocking gene may reduce lung scarring caused by radiation therapy

Eliminating a gene that regulates inflammation can significantly reduce long-term scarring caused by radiation therapy to the chest, Vanderbilt-Ingram Cancer Center investigators report.

The findings, published in the May 15 issue of the Journal of the National Cancer Institute, suggest that someday patients could avoid life-long complications of radiation therapy using drugs to block the action of this gene. Such drugs are being developed.

"Many of these patients go home on oxygen or at least unable to golf or garden or do whatever they did before," said Dr. Dennis Hallahan, professor and chairman of Radiation Oncology and professor of Biomedical Engineering. "If we can eliminate or reduce the side effects and complications of treatment, we make cancer therapy better and improve patients quality of life."

Radiation therapy delivered to the chest is often a component of treatment for patients with breast, lung, esophageal and other cancers. Virtually all these patients develop some level of lung inflammation, known as pneumonitis, which typically gets better in a matter of weeks, Hallahan said. "The radiation causes injury to the lungs and the inflammatory cells of the immune system respond as they would to a wound," he said.

However, some patients also go on to develop pulmonary fibrosis, a scarring of the lung tissue that can cause breathing problems and interfere with exercise and other physical activities.

Hallahan and his colleagues had previously demonstrated that pneumonitis could be prevented in animals by using a drug to block the action of a gene that regulates this inflammatory response. In the current study, the investigators confirmed those findings in "gene knock-out mice" engineered to lack the gene, known as intracellular adhesion molecule (ICAM1). "If you eliminate ICAM1, you eliminate the inflammatory response," Hallahan said.

So the next question to be addressed was whether the initial inflammation w

Contact: Cynthia Manley
Vanderbilt University Medical Center

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