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). Here, ERBB2 is linked to colonic neoplasm.