...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...

Data from four published datasets were analyzed to determine whether preexisting MEK1P124 mutations affect radiologic response or progression-free survival (PFS) in patients with BRAFV600-mutant metastatic melanoma treated with vemurafenib or dabrafenib...In a pooled analysis of 123 patients, the presence of a pretreatment MEK1P124 mutation (N = 12, 10%) was associated with a poorer RECIST response (33% vs. 72% in MEK1P124Q/S vs. MEK1P124 wild-type, P = 0.018), and a shorter PFS (median 3.1 vs. 4.8 months, P = 0.004).