BRAF and metastatic melanoma: These mutations were predictably accompanied by a strong up-regulation of phosphorylated MAPK/extracellular signal-regulated kinase (ERK) levels, indicative of MAPK pathway stimulation.28 Similarly, Emery et al.29 detected a MEK1P124L mutation that emerged in a resistant metastatic melanoma following patient treatment with PLX4720 (a BRAF inhibitor closely related to vemurafenib and selumetinib).29 A massively parallel sequencing study by Wagle et al.30 identified a MEK1C121S mutation in a metastatic melanoma patient who had developed clinical resistance to vemurafenib.