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Lack of melanin precursor DOPA may lead to melanoma in people with lighter skin

People with lighter skin tones may be more susceptible to melanoma not only due to a lack of UV-protective melanin, but because of a lack of the melanin precursor DOPA. That’s according to new research from the Perelman School of Medicine at the University of Pennsylvania (Penn) in Philadelphia.

This finding, published in Science Advances, may lead to improved targeted therapies for melanoma. In this mouse study, the researchers determined that DOPA inhibits the receptor CHRM1 and, further downstream, the transcription factor FOXM1. Both CHRM1 and FOXM1 are associated with more aggressive cancer.

In the study, they found darkly pigmented melanocytes contain more DOPA than lightly-pigmented melanocytes. They then determined that DOPA blocked signalling from CHRM1, inferring that a lack of DOPA in the lightly-pigmented melanocytes may lead to the development of melanoma.

“This was very exciting, as DOPA was not previously known to have anything to do with CHRM1, and because DOPA is already a [U.S.] FDA-approved agent for Parkinson’s disease,” said lead author Miriam Doepner in a press release. She is a graduate student in the lab of Todd Ridky, MD, PhD, an associate professor of dermatology at Penn and senior author of the study.

“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,” said Dr. Ridky.

“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,” he said.


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