PPIB and melanoma: B-RafV600E amplification [126], expression of B-RafV600E splice variants promoting Ras-independent dimerization (p61B-RafV600E) [30], C-Raf overexpression [116,122,127], Raf isoform signal switching [116] and increased expression of the alternative Mek kinase COT (Tpl2) [128] have all been reported and connected to inhibitor resistance in melanoma cells.