Cancer drug might help with skin disease

A drug that seems to slow down cell cancer division and induce cell death might be useful in a certain skin disease where skin cells have gone awry, researchers at Augusta University said.


In a study published online in the Journal of Investigative Dermatology, the researchers look at aquaporin-3 in skin cells, an important channel for transporting water and glycerin in the skin that is essential for hydration and healthy function. This channel is diminished in skin diseases like psoriasis or is “mislocalized” in those cells, said Dr. Vivek Choudhary, an assistant research scientist in the department of physiology and lead author on the paper.

“It is not there where it should be,” he said. “It suggests that aquaporin-3 is messed up in those (psoriasis) lesions. And it may be a causation of that.”

Another important characteristic of psoriasis is an unwanted proliferation of skin cells and some have looked toward cancer drugs such as histone deacetylase (HDAC) inhibitors, which tamp down the division of cells, as a way to address that, said Dr. Wendy Bollag, a professor of physiology at AU and a skin disease researcher.

“It had been proposed in some articles because these HDAC inhibitors were effective against diseases characterized by excessive proliferation that psoriasis might be one of the diseases that could potentially be targeted (by the drugs),” she said.

Part of the problem with using the drugs, however, is that while they hit certain factors involved in cell division, they also tend to have a widespread effect on it, which could create some unwanted consequences, Bollag said.

“It turns out that is good in the case of cancer, but it’s a sledgehammer,” she said. “It’s too broad.”

The key then was to see if there is a specific effect on cell division that can be coaxed out of using a certain inhibitor, Bollag said. In normal skin, the bottom-most layer is where cells are dividing and, as they mature and rise through to the upper layers, they are supposed to stop, she said. In psoriasis, the cells at the upper layers are also still dividing and proliferating.

“So, clearly, they are not growth-arresting properly,” Bollag said.

The researchers looked at a particular HDAC inhibitor that is already being used to treat a skin cancer known as cutaneous T-cell lymphoma. Cells treated with that inhibitor began to produce more aquaporin overall, which is a good effect, Choudhary said. It also seemed to increase the activity of an important cell growth regulator known as p53, that also seems important in regulating aquaporin, he said.

While it is not cancer, psoriasis is still a serious disease and psoriasis patients have been shown to be at higher risk for other diseases, such as cardiovascular disease, and at a higher risk for things like stroke, Bollag said. Psoriasis also has a big impact on a patient’s quality of life, she said.

“There are surveys that have shown that psoriasis patients respond in terms of quality of life similar to patients who are on chronic dialysis,” Bollag said. “It really impacts their social ability, so it is a very serious disease.”

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