However, clinical studies have shown that HER2-poszitive cancers are prone to become resistant to trastuzumab and pertuzumab; resistance mainly involves crosstalk with heterologous receptors, amplification, and the destruction of binding sites to HER2 receptors (111, 112), which may be related to the abnormal activation of the PI3K-Akt signaling pathway leading to PI3KCA mutation, phosphatase, and tensin homologue loss (113–115). Here, ERBB2 is linked to cancer.