Five MAP2K1 gene mutations (encodes the MEK1 kinase) were detected in either drug-resistance specimens (3 mutations; MEK1V60E, MEK1G128V, and MEK1V154I in Patients 41, 32, and 28, respectively) or pre-treatment tumors that progressed rapidly in the face of clinical RAF inhibition (2 mutations; MEK1P124S and MEK1P124L in Patients 4 and 15, respectively) (Fig. 1B).

...examined two BRAF-mutant melanoma cell lines with endogenous MEK1P124Q (SMU030P) and MEK1P124L (D28; ref. 34) mutations...when compared with a small panel of BRAFV600/MEK1 wild-type melanoma cell lines, the SMU030P and D28 cell lines showed intermediate sensitivity to dabrafenib, but were exquisitely sensitive to the downstream MEK and ERK inhibitors, trametinib and VX-11e...