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磷酸化蛋白质组学在激酶靶向治疗转化中的作用

Impact of phosphoproteomics in the translation of kinase-targeted therapies.

作者信息

Casado Pedro, Hijazi Maruan, Britton David, Cutillas Pedro R

机构信息

Cell Signalling and Proteomics Group, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK.

出版信息

Proteomics. 2017 Mar;17(6). doi: 10.1002/pmic.201600235. Epub 2016 Dec 23.

Abstract

Signaling pathways driven by protein and lipid kinases are altered in most human diseases. Therefore, pharmacological inhibitors of cell signaling are one of the most intensively pursued therapeutic approaches for the treatment of diseases such as cancer, neurodegeneration, and metabolic syndromes. Phosphoproteomics is a technique that measures the products of kinase activities and, with the appropriate bioinformatics techniques, the methodology can also provide measures of kinase pathway activation and network circuitry. Hence, due to recent technological advantages, LC-MS-based quantitative phosphoproteomics provides relevant information for the design and implementation of kinase inhibitor based therapies. Here, we review how phosphoproteome profiling is being used in translational research as a means to identify drug targets and biomarkers for personalizing therapies based on kinase inhibitors.

摘要

在大多数人类疾病中,由蛋白质激酶和脂质激酶驱动的信号通路都会发生改变。因此,细胞信号传导的药理学抑制剂是治疗癌症、神经退行性疾病和代谢综合征等疾病最受关注的治疗方法之一。磷酸化蛋白质组学是一种测量激酶活性产物的技术,并且通过适当的生物信息学技术,该方法还可以提供激酶途径激活和网络电路的测量方法。因此,由于最近的技术优势,基于液相色谱-质谱联用的定量磷酸化蛋白质组学为基于激酶抑制剂的治疗设计和实施提供了相关信息。在这里,我们综述了磷酸化蛋白质组分析如何在转化研究中作为一种手段,用于识别药物靶点和生物标志物,以实现基于激酶抑制剂的个性化治疗。

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