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"Our latest study is the first to demonstrate that blocking or deleting the A2A receptor can be useful in reducing radiation-induced scarring in skin," Bruce Cronstein said.
In an early study of mice, researchers at NYU Langone’s Laura and Isaac Perlmutter Cancer Center showed that a topical paste may prevent scarring and fibrosis caused by radiation therapy.
In order to mimic the development of radiation dermatitis — an adverse event experienced by as many as 95 percent of patients — the researchers exposed the skin of mice to a single dose of radiation similar to what patients with cancer would receive over five weeks. Some of the mice were normal, and the others were genetically engineered to lack the adenosine A2A protein receptor.
Their skin was then treated daily with either an adenosine A2A receptor—blocking paste or a placebo. Previous studies have shown that the A2A receptor stimulates collagen production and thus, scarring. Radiation to the skin causes skin thickening and the buildup of fibrotic tissue, which in some cases can be severe enough for patients to stop treatment.
One month after exposure, the genetically-engineered mice developed no skin reaction. Mice treated with the A2A receptor—blocking paste accumulated 10 percent more skin-thickening collagen, whereas mice that received the placebo doubled their amount of collagen, skin-thickening and fibrosis.
“Our latest study is the first to demonstrate that blocking or deleting the A2A receptor can be useful in reducing radiation-induced scarring in skin,” study author and rheumatologist, Bruce Cronstein, director, NYU Langone’s Clinical and Translational Science Institute, said in a statement.
The research team developed the A2A receptor-blocking paste using 2.5 mg of active ingredient per milliliter of 3 percent carboxymethyl cellulose, a gum “binder” used to make drugs.
If successful, further testing could potentially lead to this anti-scarring paste becoming a viable treatment to prevent fibrosis in patients with early-stage cancer.
“The study also suggests that adenosine A2A receptor—antagonists may have broad application as drug therapies for preventing fibrosis and scarring, not just in the liver but also in the skin,” Cronstein said.
He added that the new paste could be especially useful for patients in preventing or improving radiation-induced skin changes because there are very few effective drugs on the market to treat fibrosis. Additionally, the paste used in the study can be applied directly to the skin and was not associated with adverse events.
The findings also indicate that A2A antagonist drugs may be effective in treating other diseases involving the skin and connective tissues, such as scleroderma and interstitial pulmonary fibrosis.
The research team plans to study the A2A receptor further to determine the mechanism underlying its role in scarring and fibrosis.
Perez-Aso M, Mediero A, Low YC, et al. Adenosine A2A receptor plays an important role in radiation-induced dermal injury. FASEB J. 2016;30(1):457-465.