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利用蛋白质组学的力量来鉴定癌症中致癌的、可成药的信号通路。

Harnessing the power of proteomics for identification of oncogenic, druggable signalling pathways in cancer.

作者信息

Murray Heather C, Dun Matthew D, Verrills Nicole M

机构信息

a School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, Priority Research Centre for Cancer Research, Innovation and Translation , University of Newcastle , Callaghan , NSW , Australia.

b Cancer Research Program , Hunter Medical Research Institute , Newcastle , NSW , Australia.

出版信息

Expert Opin Drug Discov. 2017 May;12(5):431-447. doi: 10.1080/17460441.2017.1304377. Epub 2017 Mar 17.

Abstract

Genomic and transcriptomic profiling of tumours has revolutionised our understanding of cancer. However, the majority of tumours possess multiple mutations, and determining which oncogene, or even which pathway, to target is difficult. Proteomics is emerging as a powerful approach to identify the functionally important pathways driving these cancers, and how they can be targeted therapeutically. Areas covered: The authors provide a technical overview of mass spectrometry based approaches for proteomic profiling, and review the current and emerging strategies available for the identification of dysregulated networks, pathways, and drug targets in cancer cells, with a key focus on the ability to profile cancer kinomes. The potential applications of mass spectrometry in the clinic are also highlighted. Expert opinion: The addition of proteomic information to genomic platforms - 'proteogenomics' - is providing unparalleled insight in cancer cell biology. Application of improved mass spectrometry technology and methodology, in particular the ability to analyse post-translational modifications (the PTMome), is providing a more complete picture of the dysregulated networks in cancer, and uncovering novel therapeutic targets. While the application of proteomics to discovery research will continue to rise, improved workflow standardisation and reproducibility is required before mass spectrometry can enter routine clinical use.

摘要

肿瘤的基因组和转录组分析彻底改变了我们对癌症的理解。然而,大多数肿瘤存在多种突变,确定靶向哪个癌基因甚至哪个信号通路很困难。蛋白质组学正成为一种强大的方法,用于识别驱动这些癌症的功能重要信号通路,以及如何对其进行靶向治疗。涵盖领域:作者提供了基于质谱的蛋白质组分析方法的技术概述,并回顾了目前用于识别癌细胞中失调网络、信号通路和药物靶点的现有及新兴策略,重点关注分析癌症激酶组的能力。还强调了质谱在临床中的潜在应用。专家观点:在基因组平台上添加蛋白质组信息——“蛋白质基因组学”——正在为癌细胞生物学提供无与伦比的见解。改进的质谱技术和方法的应用,特别是分析翻译后修饰(PTMome)的能力,正在提供癌症中失调网络的更完整图景,并揭示新的治疗靶点。虽然蛋白质组学在发现研究中的应用将持续增加,但在质谱能够进入常规临床应用之前,需要改进工作流程的标准化和可重复性。

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