Novel combination therapy effective for NRAS mutant and therapy resistant melanoma

PHILADELPHIA – (April 12, 2018) – Wistar researchers have identified a novel therapeutic vulnerability in NRAS mutant melanoma and an effective strategy to address it, using a combination of two clinically relevant inhibitors, according to study results published online in EMBO Molecular Medicine.

NRAS mutant melanoma represents about 25 percent of melanoma cases. The prognosis for patients is generally poor because NRAS mutant melanoma is aggressive and resistant to most therapies. In addition, development of secondary NRAS mutations represents a mechanism of acquired resistance to targeted therapies.

“NRAS is a very attractive therapeutic target but also an extremely challenging one,” said lead researcher Jessie Villanueva, Ph.D., assistant professor in the Molecular & Cellular Oncogenesis Program at Wistar. “Despite years of efforts, we don’t yet have effective ways to block the activity of mutant NRAS, and the picture is further complicated by the heterogeneity of resistance mechanisms.”

“We have identified a novel vulnerability in NRAS-dependent melanoma and developed a combination therapy that may offer a valuable strategy to target therapy resistant melanoma,” she added.

Because NRAS and the other members of the RAS family have proven to be difficult to target directly, the most effective approach is to discover other


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