In the current study we have demonstrated that in HER2-positive gastric cancer cell lines the addition of duligotuzumab, targeting HER3 receptor, or ipatasertib, targeting AKT protein, enhances the antitumor effect of trastuzumab in vitro through a fully inhibition of the membrane signals, on HER2 and HER3, and of downstream signaling, including AKT, and MAPK pathways. The gene discussed is ERBB2; the disease is gastric cancer.