Block protein to curb melanoma’s spread

UNC-CHAPEL HILL (US) — Melanoma develops when cells called melanoblasts experience uncontrolled growth. Now researchers have identified a protein that is key to the cells’ movement.

In a new study published in Nature Communications, mice lacking the protein, P-Rex1, showed resistance to melanoma metastases. When researchers tested human melanoma cells and tumor tissue for the protein, P-Rex1 was elevated in the majority of cases.

Melanoma is one of the only forms of cancer that is still on the rise and is one of the most common forms of cancer in young adults.  The incidence of melanoma in women younger than age 30 has increased more than 50 percent since 1980. Metastases are the major cause of death from melanoma.

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“We know that mutations in a gene called BRAF are important for the development of melanoma and several years ago we published a collaborative paper listing 82 proteins that seem to be affected by this genetic pathway, says Channing Der, professor of pharmacology at University of North Carolina at Chapel Hill. “From that list, we focused on P-Rex1 in collaboration with Dr. Nancy Thomas here at UNC and researchers in the United Kingdom.”

A drug approved this summer, vemurafenib, is the first treatment directed at the BRAF mutation. Clinical trials found that the treatment offers a significant survival benefit.

“We think that vemurafenib may work, in part, by blocking the up-regulation of P-Rex1,” Der adds.

“As a physician and scientist, I know firsthand the frustration of having very limited therapeutic options to offer to patients with metastatic melanoma,” says Nancy Thomas, professor of dermatology, whose laboratory analyzed the protein’s expression in human cells. “Pinpointing that P-Rex1 plays a key role in metastasis gives us a better understanding of how vemurafenib may work and a target for developing new treatments.”

The work was led by Katherine Pedone, a postdoctoral fellow in Der’s laboratory. Researchers from the UK, France, Canada, and Switzerland collaborated on the study that was supported by the Association of International Cancer, National Institutes of Health, American Cancer Society, Cancer Research UK, and Target-Melanoma. Initial support at UNC was provided by the University Cancer Research Fund.

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