Activation of HER3 is responsible for the intrinsic resistance of lung and colon cancer cells to MEK inhibitors.26 Indeed, treatment of H358 and HCT116 cells with selumetinib resulted in induction of the active, phosphorylated form of HER3 (p-HER3), whose downstream signaling precludes efficient suppression of signaling to the ERK kinases downstream of MEK26 (Fig. 5a). Here, MAPK1 is linked to malignant colon neoplasm.