Mutations that activate the MAPK pathway are found in >30% of human cancers and as a result, efforts to develop drugs against members of the ERK cascade have been extensively pursued.7–9 Despite initial clinical response using BRAF10,11 and MEK inhibitors,12,13 the rapid rise of resistance has limited the durability of BRAF/MEK drugs.14 Reactivation of ERK signaling in tumors resistant to BRAF/MEK inhibitors has prompted interest in targeting these downstream kinases directly for cancer therapy.15,16. This evidence concerns the gene MAPK1 and cancer.