RAF1 and melanoma: Recent studies demonstrated that MAPK-dependent acquired resistance to B-RAF inhibition in melanomas can involve (i) upregulation of receptor tyrosine kinases (RTKs) and N-RAS [44]; (ii) elevated expression of COT kinase through MAPK pathway reactivation [45]; (iii) activation of MAPK kinase (MEK aka MAPK/ERK) [46, 47]; (iv) elevation of C-RAF [48].