woman for radiation
Photo by Rhoda Baer
A topical paste can reduce fibrosis caused by radiation therapy, according to preclinical research published in The FASEB Journal.
The study addressed a type of fibrosis called radiation dermatitis, in which radiation applied to the skin causes the buildup of fibrotic tissue and skin thickening.
To test their topical paste, researchers mimicked the development of radiation dermatitis in mice.
They exposed the mice’s skin to a single dose of 40 Gy, an amount of radiation similar to what patients undergoing anticancer radiation typically receive over 5 weeks.
Some of the irradiated animals were wild-type mice, while others were genetically engineered to lack the A2A receptor (A2AR). The researchers had previously shown that occupancy of A2AR induces collagen production.
The wild-type mice went on to receive placebo or daily treatment with ZM241385, a paste made with the research team’s patented A2AR blocker. The paste contains 2.5 milligrams of active ingredient per milliliter of 3% carboxymethyl cellulose, a gum “binder.”
A month after exposure, wild-type mice that received placebo had a nearly 2-fold increase in the amount of collagen and skin thickness. These mice also experienced epithelial hyperplasia.
On the other hand, mice treated with ZM241385 accumulated only 10% more skin-thickening collagen. ZM241385 treatment reduced the number of myofibroblasts, collagen fibrils, proliferating keratinocytes, and angiogenesis when compared to placebo. And the paste prevented epithelial hyperplasia.
Like ZM241385-treated mice, A2AR knockout mice did not have the excessive collagen production and skin thickening observed in placebo-treated wild-type mice. The knockout mice also exhibited reductions in myofibroblast content, angiogenesis, and epithelial hyperplasia.
The researchers noted that radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2AR knockout mice.
“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,” said study author Bruce Cronstein, MD, of New York University School of Medicine in New York, New York.
“The study also suggests that adenosine A2A receptor antagonists may have broad applications as drug therapies for preventing fibrosis and scarring, not just in the liver but also in the skin.”
If further experiments prove successful, Dr Cronstein said, clinicians treating early stage cancers with radiation could eventually prescribe an A2AR inhibitor paste to prevent fibrosis. He said his team next plans to study the mechanism underlying A2AR’s role in fibrosis.
