We ascertained that there are two possible MEK1/2-inhibitor response “classes” within pan-negative melanomas (Table 1, Figure 5): Class I pan-negative responders behave like BRAF V600-mutant cells in that they are highly sensitive to MEK1/2 inhibition and downregulation of phosphorylated MEK1/2 and ERK1/2 is observed. Here, MAPK3 is linked to melanoma.