Triulzi Tiziana, Bianchi Giulia Valeria, Tagliabue Elda
Molecular Targeting Unit, Department of Experimental Oncology & Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Future Oncol. 2016 Jun;12(11):1413-28. doi: 10.2217/fon-2015-0025. Epub 2016 Mar 23.
The transmembrane tyrosine kinase receptor HER2 is overexpressed in 20% of invasive breast cancers and is associated with more aggressive disease. Until the advent of targeted agents, HER2 was associated with worse outcome. Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, combined with chemotherapy improves disease-free and overall survival in both primary and metastatic tumors and represents a foundation of care for patients with HER2-positive breast cancers. However, a sizeable number of patients do not respond to this reagent, indicating the need for a biomarker able to recognize resistant tumors. Here, we review various studies on mechanisms of action and resistance to trastuzumab that have proven relevant in understanding how tumor care can be tailored to all HER2-positive patients.
跨膜酪氨酸激酶受体HER2在20%的浸润性乳腺癌中过表达，且与更具侵袭性的疾病相关。在靶向药物出现之前，HER2与较差的预后相关。曲妥珠单抗是一种重组人源化抗HER2单克隆抗体，与化疗联合使用可改善原发性和转移性肿瘤患者的无病生存期和总生存期，是HER2阳性乳腺癌患者治疗的基础。然而，相当一部分患者对该药物无反应，这表明需要一种能够识别耐药肿瘤的生物标志物。在此，我们综述了各种关于曲妥珠单抗作用机制和耐药性的研究，这些研究已被证明与理解如何为所有HER2阳性患者量身定制肿瘤治疗相关。
