A type of drug that is commonly used to treat epileptic seizures may slow or prevent uveal melanoma from metastasizing to other parts of the body, according to a study in the October 28 online version of Clinical Cancer Research.
Photo: Mark T. Dunbar, O.D.
The researchers determined that FDA-approved anti-epileptic drugs known as histone deacetylase (HDAC) inhibitors alter the way that the aggressive form of uveal melanoma expresses its key genes. According to the researchers, uveal melanoma is very aggressive and typically spreads from the eye to other bodily organs, such as the liver.
“HDAC inhibitors appear to reverse the aggressive molecular signature that we had identified several years ago as a marker for metastatic death,” said lead researcher J. William Harbour, M.D., distinguished professor of ophthalmology and visual sciences and professor of biology and molecular oncology at Washington University School of Medicine in St. Louis. “When we look at aggressive melanoma cells under the microscope after treatment with HDAC inhibitors, they look more like normal cells and less like tumor cells.”
Treatment with HDAC inhibitors may allow patients with such aggressive melanomas to live for many years without any detectable metastasis, Dr. Harbour predicted.
“Melanoma in general, and uveal melanoma in particular, is notoriously difficult to treat once it has metastasized and grown in a distant organ,” he added. “I suspect that the best role for HDAC inhibitors will be to slow or prevent the growth of tumor cells that have spread out of the eye, but cannot yet be detected. This might lengthen the time between the original eye treatment and the appearance of detectable cancer in the liver and elsewhere.”
In addition, HDAC inhibitors cause only relatively mild side effects such as drowsiness, Dr. Harbour explained.
Clinical trials on patients with metastatic uveal melanoma could begin within the next six to 12 months, he noted.
Landreville S, Agapova OA, Matatall KA, et al. Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. Clin Cancer Res. 2011 Oct 28. [Epub ahead of print]
