Dartmouth researchers have found that the genetic mutation BRAFV600E, frequently found in metastatic melanoma, not only secretes a protein that promotes the growth of melanoma tumor cells, but can also modify the network of normal cells around the tumor to support the disease's progression. Targeting this mutation with vemurafenib reduces this interaction, and suggests possible new treatment options for melanoma therapy. They report on their findings in “BRAFV600E melanoma cells secrete factors that activate stromal fibroblasts and enhance tumorigenicity,” which was recently published in the British Journal of Cancer.
Using genetically engineered melanoma cell lines and xenograft mouse models, the Dartmouth researchers found that BRAFV600E melanoma cells expressed higher levels of several cytokines (proteins that act on the immune system and can be used to help the body fight cancer) and matrix metalloproteinase-1 (MMP-1; MMPs are associated with various processes including tissue repair and metastasis). Their study also suggests a mechanistic link between BRAFV600E and MMP-1 that modifies the network of normal cells surrounding melanoma tumors, making these “normal cells” more supportive of tumor growth and development. Vemurafenib, a therapeutic drug that specifically targets the BRAFV600E mutation, is able to reduce the expression of several proteins essential for activating this 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,” says study co-author Chery A. Whipple, PhD, research associate at the Geisel School of Medicine at Dartmouth. “If so, does it create a window of time where we could target the TME, normalize it, and enhance the patient's therapeutic response?” Read the study abstract.
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