Mechanism of trastuzumab resistance and its reversal strategy

It has been proved that the breast cancer and gastric cancer could be therapeutically targeted by trastuzumab, while the resistance of which seriously decreased the efficacy. Several mechanisms of resistance have been clarified as follows:p95HER2 overexpression, PI3K-AKT pathway constitutively activation, HER family receptor-mediated signal transduction up-regulation, and non-HER family growth factor receptor-mediated signal transduction upregulation. Some novel targeted agents, such as lapatinib, T-DM1, pertuzumab, everolimus, offer new options for trastuzumab-resistant patients.