乳腺癌患者对曲妥珠单抗的耐药机制与治疗策略

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

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、曲妥珠单抗一药物共轭物。

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 trastuzumah 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 （HSPg0） and CD44. Additionally, potential strategies for overcoming resistance to trastuzumab include using new targeted medicines, such as pertuzumab, lapatinib and trastuzumab-DM1.