NRAS and melanoma: This co-regulatory response may also exist in cells that are chronically exposed to Trametinib, as NRAS-mRNA expression was upregulated 2-fold when comparing the Trametinib-resistant NRAS-mutant melanoma cell lines D04RM and MM415RM to their according parental cell lines from which they had originated (Fig. 4d, resistance was acquired through chronic exposure to increasing Trametinib concentrations.