Notably, all tested cell lines carrying BRAF fusions were resistant to vemurafenib and dabrafenib, sharply distinguishing them from BRAFV600E mutant cell lines…although they harbored the exact same AGK-BRAF fusion. Globally, the C022 cell line showed a higher level of resistance to the tested drugs than C0902 (Figure 4a).

The AGK-BRAF expressing C0902 cell line showed increased sensitivity to the type II RAF inhibitor sorafenib (IC50 = 410 nM) compared to the BRAFV600E mutant melanoma cell lines A375 (IC50 = 3.0 µM) and SK-MEL-28 (IC50 = 3.1 µM). In contrast, the C0902 cell line showed relative resistance to the type I inhibitor vemurafenib (IC50 = 5.0 µM) compared to the BRAFV600E mutant cell lines (IC50 = 80–92 nM) (Figure 3c).