Further research on one of the pan-negative melanoma samples revealed a fusion between two genes - PAPSS1 and BRAF. Additional analysis of 24 pan-negative samples revealed one other BRAF fusion between the genes TRIM24 and BRAF.
The investigators then discovered that both of these BRAF fusions triggered a pathway in melanoma cancer cells called the MAPK signaling pathway.
Some of the cancer cells were then treated with vemurafenib - a BRAF inhibitor. Others were treated with trametnib - a drug that erases a protein called MEK in the MAPK pathway.
The researchers discovered that the MAPK signaling pathway triggered by the BRAF fusions could be inhibited by trametnib. This indicated that the fusions were able to make melanoma cells sensitive to MEK inhibitors.
The MAPK signaling pathway did not show any response to vemurafenib.
Prof. Sosman, also an investigator of the Stand up to Cancer Melanoma Dream Team, says the discovery of the BRAF fusions suggest there may already be drugs available to treat these pan-negative melanomas.
He explains:
0 comments:
Post a Comment