曲妥珠单抗原发耐药及继发性耐药的分子机制

Molecular mechanisms of drug resistance of trastuzumab

曲妥珠单抗是目前治疗HER-2阳性乳腺癌的主要靶向药物,在乳腺癌的各阶段与化疗联合能够明显增加疗效,降低复发转移风险,延长患者生存期。但并非所有患者都获益,原因是存在初始治疗无效的原发性耐药和治疗过程中产生的继发性耐药。对曲妥珠单抗耐药机制的研究发现,HER-2分子空间结构及下游信号通路的改变均可能导致曲妥珠单抗的耐药。本文综述曲妥珠单抗可能的耐药机制,为下一步筛选出能够预测曲妥珠单抗疗效的生物学指标提供基础。

Trastuzumab currently is main target drug being used to treat positive HER-2 mastocarcinoma,which could significantly increase efficacy combining with chemotherapy during each stage of the development of mastocarcinoma and reduce recurrence risk and prolong with the survival period of the patient.But not all the patients could obtain benefit from it because of the existing primary drug resistance of initial treatment ineffectiveness and secondary drug resistance occurred during the treatment.It was founded in the study on the drug resistance mechanism of trastuzumab that the change of the space structure of HER-2 molecular and the change in the downstream signal channel all could cause the drug resistance of trastuzumab.In this paper,the possible drug resistance mechanisms of trastuzumab were reviewed,and established basis for further screening out the biology index which could predict the therapeutic effect of trastuzumab.