NRAS and melanoma: In our previous publication, we have shown that both BRAF- and NRAS-mutant melanoma cell lines significantly upregulated ERK5 signaling when subjected to MEKi using trametinib, selumetinib, binimetinib or cobimatinib, or ERK1/2 inhibition (ERKi) using GDC-0994 [37] (Figure 5).