However, trastuzumab treatment effects are not ideal in some patients with advanced HER2-positive GC, which may be related to intratumoral HER2 heterogeneity (46, 47), loss of HER2 expression after treatment (48), gene amplification mutations (49, 50), and abnormal intracellular signaling (RTK–RAS–PI3K) (51). Here, ERBB2 is linked to gastric cancer.