Given the observed concomitant activation of MAPK and PI3KCA-driven intracellular signals in HER2-amplified colon cancer cells, we next evaluated the cell growth inhibiting effects of a selective MEK1/2 inhibitor, refametinib, and of a selective PI3Kα inhibitor, pictilisib, as single agents or in combination. This evidence concerns the gene MAP2K1 and malignant colon neoplasm.