抗体药物偶联物阿多曲妥珠单抗依酯研究进展

Antibody drug conjugate ado trastuzumab emtansine:an updated review

作为抗肿瘤药的全新设计策略,抗体药物偶联物是近年来广受关注的研究热点。2013年,阿多曲妥珠单抗依酯(ado trastuzumab emtansine,T-DM1,Kadcyla)成功上市,为耐曲妥珠单抗的HER2+晚期乳腺癌患者的二线治疗提供了全新的解决方案。基于该药优异的临床表现和HER2在多种肿瘤中的高表达,罗氏公司进一步尝试拓展其用于HER2+乳腺癌各线治疗和早期乳腺癌的新辅助治疗,以及胃癌和非小细胞肺癌的治疗。总体来说,结果有喜有忧,包括其二线用药地位进一步确立,但肿瘤异质性等因素仍带来极大挑战。本文综述了Kadcyla在机制及临床方面的研究进展。

As a new design strategy of anticancer drugs,antibody-drug conjugates have become a research hotspot in recent years. In 2013,the successful launch of ado trastuzumab emtansine（Kadcyla）provided a new solution for second-line treatment with trastuzumab-resistant HER2-positive advanced breast cancer patients. Based on its excellent clinical performance and HER2′s overexpressing in many tumors,Roche further attempts to expand it for the therapy of HER2-positive metastatic breast cancer of each line and neoadjuvant for early breast cancer treatment,as well as applications to gastric cancer and non-small cell lung cancer（NSCLC）treatment. In general,results are mixed. Its position as second-line drugs of is further established,but factors such as tumor heterogeneity are still a big challenge. This paper reviews the recent progress in these areas after its launch.