RAF1 and melanoma: Resistance pathways discovered in melanoma can be divided broadly into three groups: RTK hyperactivation/overexpression, secondary MAPK/ERK mutations (ERK1/2 phosphorylation through NRAS mutations, paradoxical MAPK activation, AKT amplification/mutation, CRAF dimerization, BRAF amplification) and other alternative pathways (cyclin D1 induction, PTEN loss, BIM suppression) (73).