乳腺癌患者对曲妥珠单抗的耐药机制与治疗策略

 曲妥珠单抗在治疗人类表皮生长因子受体2（Her-2）过表达的乳腺癌患者中存在耐药现象，其耐药的可能机制，包括曲妥珠单抗与Her-2受体有效结合受阻；多种旁路途径激活下游通路，如胰岛素样生长因子1受体(IGF-1R)途径，肝细胞生长因子受体(HGFR)途径；人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)缺失导致下游信号通路异常；磷脂酰肌醇激酶-3催化亚单位α基因(PIK3CA)突变；热休克蛋白90(HSP90)及CD44过度表达等。针对曲妥珠单抗耐药的可能治疗策略，包括使用新一代的靶向药物，如帕妥珠单抗、拉帕替尼、曲妥珠单抗-药物共轭物。

Resistance mechanisms of trastuzumab and treatment strategies in patients with breast cancer

In the treatment of human epidermal growth factor receptor 2 (Her-2) overexpressing breast cancer, some patients have drug resistance to trastuzumab. Potential mechanisms of resistance to trastuzumab include impaired access of trastuzumab to Her-2; alternative signaling from insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor receptor (HGFR) and so on; aberrant downstream signaling caused by loss of phosphatase and tensin homologs deleted from chromosome 10 (PTEN); phosphatidylinositol 3-kinase catalytic alpha polypeptide gene (PIK3CA) mutation; over-expression of heat shock protein 90 (HSP90) and CD44. Additionally, potential strategies for overcoming resistance to trastuzumab include using new targeted medicines, such as pertuzumab, lapatinib and trastuzumab-DM1.