BRAF and melanoma: Numerous studies, largely in melanoma, have demonstrated that successful targeting of the MAPK signaling cascade is dependent on discrete, mutation-specific response to inhibitors among wild-type BRAF, BRAF-V600E and mutant-RAS tumors [16-18, 41] This is partly due to altered protein-protein interactions, RAF-heterodimerization, and kinase-substrate interactions as well as reorganization of a highly dynamic signaling network in response to targeted inhibitors [42].