摘要Human epidermal growth factor receptor 2(HER2)is over-expressed in 20%-25% of invasive breast cancer and is associated with an aggressive tumor phenotype and reduced survival rate.As a clinically widely applied HER2-targeted monoclonal antibody,trastuzumab(Herceptin(R)),combined with chemotherapy significantly increases the no tumor survival time of the patient.However,the majority of the cancers that initially respond to Herceptin begin to counter against the treatment within 1 year.This review describes several important well-known trastuzumab resistance mechanisms as well as the updated advancement in this field.The sufnciently investigated mechanisms are over-activation of PI3K/AKT pathway,activation of PI3K/AKT via alternative pathway,steric hindrance of receptor-antibody interaction,increase of serum HER2 extracellutar domain,and abnormal expression of epidermal growth factor receptor(EGFR)family and their ligands.And the newly investigated mechanisms involve Darpp-32 and t-Darpp,autophagy of tumor cells,HSP27,HSP90,c-MYC,ADAM proteases,EphA2,Racl,MUC1*,HER2△16,and mesenchymal CD44(pos)CD24(neg/low)phenotype.