Based on these data, in order to inhibit the compensatory feedback effect due to activation of downstream signaling pathways, we have tested as therapeutic strategy the combination of two selective MEK and PI3KCA inhibitors, refametinib and pictilisib, respectively, in HER2-amplified colon cancer cells (LIM1215-HER2 and SW48-HER2). The gene discussed is ERBB2; the disease is malignant colon neoplasm.