New research has outlined the exact process by which UVB radiation from the sun can cause melanoma.
New research suggests that deficient levels of a protein called retinoid-X-receptor (RXR) may cause normal healthy skin cells to turn into melanoma cells.
The findings, published today in PLOS Genetics, may help pave the road toward novel melanoma prevention and treatment modalities. “The lower the level of the RXR protein in the melanocytes, the higher the chances of melanoma development and progression,” says study author Arup Indra, PhD, an associate professor in the Department of Pharmaceutical Sciences at Oregon State University and Oregon Health & Science University in Corvallis, Ore, in an interview with Plastic Surgery Practice. “We believe this is a breakthrough in understanding exactly what leads to cancer formation in melanoma.”
“We believe this is a breakthrough in understanding exactly what leads to cancer formation in melanoma.” —Arup Indra, PhD
The reason that this protein has not been identified before via large-scale genome-wide associations may be that it is epigenetically controlled by ultraviolet light, he speculates. It may also be a co-conspirator with BRAF, he says. “This can be happening, and it is difficult to get picked up by assays.”
To arrive at the findings, Indra and colleagues created knockout animal models to better eludicate the role of RXR in melanocytes.
Understanding RXR’s Role in Skin Cancer
Melanocytes and keratinocytes routinely suffer genetic damage, but sometimes the damage can be repaired. At other times, the immune response – in the presence of adequate levels of RXR in the melanocytes – will kill the defective skin cells before they become malignant.
When expressed levels of RXR in the melanocytes are too low, this protective process breaks down. The chemicals that can help control mutated cells are actually suppressed, and the conditions for cancer are promoted. “It’s the breakdown of these control processes that result in cancer, and that happens when RXR levels get too low,” he says.
More research is needed to confirm the new findings and better understand their implications. In the future, a diagnostic test to determine when RXR levels are lower than they should be may be developed. As far as prevention, there may be role for diet, he says. “Certain foods, such as broccoli, may help restore RXR levels.” In addition, “We may be able to restore RXR levels by introducing the protein back into the skin cells,” he says.
Mona Mofid, MD, a dermatologist in San Diego and the medical director of the American Melanoma Foundation, reviewed the new study for PSP. “Current estimates are that 1 in 50 persons in America will develop melanoma, and they have been steadily increasing, with roughly one person dying every hour in this country from the disease,” she says. “The past few years have been very exciting for the field with the addition of several agents to the therapeutic armamentarium. The nuclear hormone receptor RXR represents a novel therapeutic target for melanoma.”
She adds that, “The results of this study may lead to early detection of melanoma, identification of high-risk patients, and potentially more effective and combined targeted strategic therapies.”
The new study was supported by the National Institutes of Health.
