泛素-蛋白酶体系统作为抗癌治疗靶点的最新进展

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Yeon Jung Kim, Yeonjoo Lee, Hyungkyung Shin, SuA Hwang, Jinyoung Park, Eun Joo Song
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引用次数: 3

摘要

由于泛素-蛋白酶体系统(UPS)调节着几乎所有的生物过程,UPS成分的失调或异常表达会导致包括癌症在内的许多病理疾病。自2003年FDA首次批准蛋白酶体抑制剂硼替佐米用于治疗多发性骨髓瘤(MM)以来,UPS一直是一个活跃的研究领域,以寻找抗癌治疗的新靶点。在这里,我们总结了新描述的UPS组件,包括E3泛素连接酶,去泛素酶(DUBs)和免疫蛋白酶体,其功能障碍导致肿瘤发生,其抑制剂自2020年以来已在临床试验中作为抗癌治疗进行了研究。我们深入解释了几种抑制剂的机制和作用,以更好地理解靶向UPS组件用于癌症治疗的优势。此外,我们描述了克服一些启动的蛋白酶体抑制剂的耐药性和有限疗效的尝试,以及一种新兴的基于protac的靶向UPS组件的抗癌治疗工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ubiquitin–proteasome system as a target for anticancer treatment—an update

Ubiquitin–proteasome system as a target for anticancer treatment—an update

As the ubiquitin–proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA’s first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy.

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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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