BRAF and melanoma: Mechanistically, targeted therapy mainly involves the inhibition of the MAPK signaling pathway by using BRAF or MEK inhibitors, alone or in combination [21], as suggested by: A) activating mutations in BRAF and NRAS oncogenes in 48% and 15% of all diagnosed melanomas, respectively [22]; and B) multiple MAPK reactivation mechanisms that confer resistance to BRAF inhibitors [23–25].