Valabrega G, Montemurro F, Aglietta M
University Division of Medical Oncology and Haematology, Institute for Cancer Research and Treatment, Strada Provinciale 142, 10060 Candiolo, Torino, Italy.
Ann Oncol. 2007 Jun;18(6):977-84. doi: 10.1093/annonc/mdl475. Epub 2007 Jan 17.
Trastuzumab is a humanized mAb directed against the extracellular domain of the tyrosine kinase receptor HER2. Trastuzumab has shown clinical activity in HER2-overexpressing breast cancers and, at present, is currently approved for patients whose tumours have this abnormality, in both the metastatic and the adjuvant setting. Several issues about its optimal use, however, are still unresolved. One of the reasons for these uncertainties lies in the absence of conclusive data about its mechanism of action and possible primary or acquired resistance mechanisms. Therefore, clinical questions such as how to optimize patient selection, how to prevent resistance to trastuzumab, or what is the optimal management of those patients whose tumours progress during treatment still await convincing answers. This review summarises the current knowledge on the preclinical and clinical evidence about the mechanism of action of trastuzumab and on the mechanisms underlying the development of resistance and also briefly discusses their possible clinical implications.
曲妥珠单抗是一种针对酪氨酸激酶受体HER2细胞外结构域的人源化单克隆抗体。曲妥珠单抗已在HER2过表达的乳腺癌中显示出临床活性，目前已被批准用于肿瘤存在这种异常的转移性和辅助性治疗的患者。然而，关于其最佳使用的几个问题仍未得到解决。这些不确定性的原因之一在于缺乏关于其作用机制以及可能的原发性或获得性耐药机制的确凿数据。因此，诸如如何优化患者选择、如何预防对曲妥珠单抗的耐药性，或者对于那些在治疗期间肿瘤进展的患者的最佳管理方法等临床问题仍有待令人信服的答案。本综述总结了目前关于曲妥珠单抗作用机制的临床前和临床证据以及耐药性产生机制的现有知识，并简要讨论了它们可能的临床意义。
