By interrogating gene expression profiles from multiple cell lines of diverse tumor types, Dry and colleagues identified two signatures: (1) an 18-gene “MEK-functional-activation” signature, indicating pathway activity independent of the mutational status of BRAF/RAS; (2) a 13-gene “compensatory-resistance” signature, predicting resistance to the MEK1 and MEK2 inhibitor selumetinib in the presence of active MEK and independently of PI3K mutational status, indicating the existence of compensatory signaling from RAS effectors other than PI3K [86]. Here, MAP2K1 is linked to neoplasm.