The rationale for combining these drugs is that several proteins, which are linked to melanoma cell response and resistance to BRAFV600/MEK-targeting agents, are HSP90 clients including ARAF, CRAF, BRAFV600E, CDK4, COT, IGF1R, PDGFR-β and AKT [16, 70, 71]. This evidence concerns the gene RAF1 and melanoma.