Research links genetic mutation, melanoma progression

Researchers at Dartmouth College have discovered that BRAFV600E, often found in metastatic melanoma, is capable of modifying normal cells surrounding the tumor to encourage disease progression.

The study also established that targeting the mutation with vemurafenib (Zelboraf, Genentech) helps to reduce the interaction that causes the disease progression, according to a news release. The researchers used genetically engineered melanoma cell lines and xenograft mouse models in their study, and discovered that BRAFV600E melanoma cells demonstrated higher levels of several cytokines and matrix metalloproteinase-1 (MMP-1).

There was a link between the genetic mutation and MMP-1 that caused the “normal cells” around melanoma tumors to support and develop tumor growth, the study suggested. Vemurafenib, though, can reduce the expression of certain proteins responsible for activating the interaction.

“Given that our data show that vemurafenib is able to reduce the expression of several proteins that are essential for activating the tumor microenvironment (TME), a next step would be to ask whether vemurafenib normalizes the TME or keeps it from becoming activated,” Chery A. Whipple, Ph.D., research associate at Dartmouth’s Geisel School of Medicine, said in the news release. “If so, does it create a window of time where we could target the TME, normalize it and enhance the patient’s therapeutic response?”

Study findings were published online in the British Journal of Cancer.

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