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从蛋白质组学角度看癌症药物耐药性的分子机制

Molecular insights into cancer drug resistance from a proteomics perspective.

机构信息

a West China School of Basic Medical Sciences & Forensic Medicine , Sichuan University , Chengdu , PR China.

b Department of Oncology , The Second Affiliated Hospital of Hainan Medical University , Haikou , P.R. China.

出版信息

Expert Rev Proteomics. 2019 May;16(5):413-429. doi: 10.1080/14789450.2019.1601561. Epub 2019 Apr 12.

Abstract

Resistance to chemotherapy and development of specific and effective molecular targeted therapies are major obstacles facing current cancer treatment. Comparative proteomic approaches have been employed for the discovery of putative biomarkers associated with cancer drug resistance and have yielded a number of candidate proteins, showing great promise for both novel drug target identification and personalized medicine for the treatment of drug-resistant cancer. Areas covered: Herein, we review the recent advances and challenges in proteomics studies on cancer drug resistance with an emphasis on biomarker discovery, as well as understanding the interconnectivity of proteins in disease-related signaling pathways. In addition, we highlight the critical role that post-translational modifications (PTMs) play in the mechanisms of cancer drug resistance. Expert opinion: Revealing changes in proteome profiles and the role of PTMs in drug-resistant cancer is key to deciphering the mechanisms of treatment resistance. With the development of sensitive and specific mass spectrometry (MS)-based proteomics and related technologies, it is now possible to investigate in depth potential biomarkers and the molecular mechanisms of cancer drug resistance, assisting the development of individualized therapeutic strategies for cancer patients.

摘要

化疗耐药和特定有效分子靶向治疗的发展是当前癌症治疗面临的主要障碍。比较蛋白质组学方法已被用于发现与癌症药物耐药相关的潜在生物标志物,并产生了许多候选蛋白,为新的药物靶点识别和治疗耐药性癌症的个体化医学提供了广阔的前景。

涵盖领域

本文综述了癌症药物耐药性的蛋白质组学研究的最新进展和挑战,重点介绍了生物标志物的发现,以及对与疾病相关的信号通路中蛋白质相互关系的理解。此外,还强调了翻译后修饰(PTMs)在癌症药物耐药机制中的关键作用。

专家意见

揭示蛋白质组图谱的变化和 PTMs 在耐药性癌症中的作用是破解治疗耐药机制的关键。随着基于灵敏和特异的质谱(MS)的蛋白质组学和相关技术的发展,现在可以深入研究潜在的生物标志物和癌症药物耐药的分子机制,为癌症患者制定个体化的治疗策略提供帮助。

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