The potential mechanisms of resistance to trastuzumab not only involves steric effects, such as the structural mutation in HER2 protein, but the alternative elevations of other tyrosine kinase receptors, such as insulin-like growth factor receptor (IGFIR), or the intracellular alterations in growth factor downstream signaling like constitutive activity of PI3K/Akt pathway [70].These findings imply that cancer cells, by utilizing other growth factor signaling, can compensate for the inhibition of HER2 signaling mediated by trastuzumab. This evidence concerns the gene ERBB2 and cancer.