Washington: Researchers have identified two novel BRAF fusions in melanomas previously considered to be negative for molecular targets, and that melanomas with these fusions were found to be potentially sensitive to anticancer drugs called MEK inhibitors.
According to Dr Jeffrey A. Sosman, professor of medicine at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, said that after performing a sophisticated analysis called targeted next-generation sequencing, it appears that about 8 percent of pan-negative melanomas have BRAF fusions.
In a pan-negative melanoma sample from one of their patients, Drs. Sosman and William Pao, M.D., Ph.D., a 2009 Stand Up To Cancer Innovative Research Grant recipient, and their colleagues identified a fusion between two genes, PAPSS1 and BRAF, which they called PAPSS1-BRAF.
They then evaluated melanomas from an additional 51 patients, 24 of which were pan-negative. In one of these 24 pan-negative samples, they identified a second novel BRAF fusion, called TRIM24-BRAF.
The investigators found that both BRAF fusions activated a pathway in the cancer cells called the MAPK signaling pathway. They then treated these fusion-bearing cells either with the BRAF inhibitor vemurafenib or with trametinib, a drug that inhibits a protein in the MAPK signaling pathway called MEK.
They found that signaling induced by the BRAF fusions was not responsive to vemurafenib but could be inhibited by trametinib, which led them to suggest that the novel fusions they identified could make melanoma cells harboring them sensitive to MEK inhibitors.
The study has been published in journal Clinical Cancer Research.