Potential new therapeutic targets to treat melanoma

Penn Medicine research shows that a relative lack of DOPA, and not simply susceptibility to sun damage, helps explain why melanoma is much more common in people with light skin tones.

People with light skin tones are far more likely to develop melanoma skin cancer than people with dark skin tones. This large disparity results from far more than can be explained by the UV protective effects of melanin pigment, and results in large part from the melanin precursor DOPA, and its ability to inhibit CHRM1, according to new research from the Perelman School of Medicine. The researchers also found that inhibiting FOXM1, a transcription factor downstream of CHRM1, also inhibits melanoma. These findings highlight two new potential therapeutic targets for melanoma, and show that it may be possible to repurpose the main medicine for Parkinson’s disease, levodopa, to inhibit melanoma. The study is published in Science Advances.

A doctor checks a person’s arm for melanoma with a hand-held scanning device.

“For decades, dermatologists and melanoma researchers thought that the particular susceptibility to melanoma in lightly pigmented skin resulted from a relative lack of protection against UV damage from the sun. This work shows that the biology is far more complex,” says Todd Ridky, an associate professor of dermatology and senior author of the study. “Not only does this research offer significant potential for new melanoma therapies, it also markedly expands the classical paradigm of melanocyte function and melanoma pathobiology.”

Every year, roughly 100,000 people are diagnosed with melanoma in the United States, according to the National Cancer Institute. Melanoma is also the type of skin cancer most likely to spread to other parts of the body and, on a case by case basis, the most likely to be deadly.

For years, researchers have linked melanin and skin pigmentation to the likelihood of developing melanoma. Melanoma risk is at least 30 times higher in individuals whose skin is more lightly pigmented compared to peers whose skin is darkly pigmented.

Read more at Penn Medicine News.