Anti-Scarring Topical Paste Reduces Radiation Fibrosis

A new study suggests that topical application of an A2A receptor (A2AR) antagonist prevents radiation dermatitis, and may be useful in the reduction of fibrotic changes in the skin.

Researchers at NYU Langone Medical Center (New York, NY, USA) conducted a study in mice to test if blocking the A2AR site could prevent radiation-induced fibrosis, a side effect experienced by as many as 95% of patients undergoing initial radiation treatment. To do so, they exposed mice to a single dose of 40 Gy, an amount of radiation similar to a five week radiation therapy treatment protocol. Some of the irradiated animals were normal; some were genetically engineered to lack A2AR, while others were treated with the A2AR antagonist ZM241385.

The results showed that in irradiated normal mice treated with the A2AR antagonist there was a marked reduction in collagen content, myofibroblast cells, angiogenesis, and density of collagen fibrils. Epidermal thickness due to an increasing the number of proliferating keratinocytes was also prevented by ZM241385. Similar changes were seen in the A2AR genetically modified mice. The study was published in the January 2016 edition of the Journal of the Federation of American Societies for Experimental Biology (FASEB).

“A2A antagonist drugs could also be used in treating other diseases involving changes in the structure of collagen, a major component of skin and connective tissues, such as scleroderma and interstitial pulmonary fibrosis,” said senior author Prof. Bruce Cronstein, MD, director of the NYU Langone Clinical and Translational Science Institute. “Such therapies are badly needed because very few drugs are currently available to treat fibrosis, and those that are on the market are not very effective.”

Radiation dermatitis is a cutaneous lesion induced by ionizing radiation, which ranges from a mild rash to severe ulceration, with approximately 85% of all patients treated with radiation therapy (RT) experiencing a moderate-to-severe skin reaction. Once considered to be a major risk of conventional RT, it has become less common and less severe since the 1970s, with the development of high- and medium-energy accelerators.

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