NF1 mutations were observed in B-RAF-mutant tumor cells that are intrinsically resistant to RAF inhibition and in melanoma tumors obtained from patients exhibiting resistance to vemurafenib, thus demonstrating the clinical potential for NF1-driven resistance to RAF/MEK-targeted therapies.

However, cells from Braf/Nf1 mutant tumors were insensitive to this agent (Fig. 4A, IC50>10µM). Biochemical studies confirmed that increasing concentrations of PLX4720 effectively suppressed phospho-ERK levels in Braf mutant cells (Fig. 4B). Notably, however, phospho-ERK was not as effectively suppressed in Braf/Nf1 mutant cells (Fig. 4B).