涉及 HSP90 抑制剂的抗癌联合疗法:临床和临床前进展综述

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL Archives of Pharmacal Research Pub Date : 2024-04-17 DOI:10.1007/s12272-024-01494-1
Yajun Liu, Chenyao Li, Hongwei Liu, Shutao Tan
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引用次数: 0

摘要

分子伴侣热休克蛋白 90(HSP90)通过驱动关键信号元件的成熟来调节癌症中的多种关键信号通路,从而在癌症的肿瘤发生和耐药性方面发挥关键作用。抑制 HSP90 会导致其客户蛋白的构象崩溃和蛋白酶体降解。目前,针对 HSP90 的小分子抑制剂的研发工作已经投入了大量精力,并对 20 多种抑制剂进行了癌症治疗临床试验评估。然而,由于器官毒性和耐药性等缺点,目前只有一种 HSP90 抑制剂被批准用于临床。近年来,与其他抗癌疗法联合使用的 HSP90 抑制剂在治疗癌症方面显示出了巨大的潜力。HSP90 抑制剂与各种抗癌疗法(包括化疗、靶向治疗、放疗和免疫疗法)协同作用。HSP90 抑制剂可以改善上述疗法的药理作用,减少耐药性。本综述概述了过去十年中报道的临床和临床前研究中使用 HSP90 抑制剂和其他抗癌疗法进行联合治疗的情况,并总结了这些联合疗法的设计策略和前景。总之,本综述为进一步研究和应用这些联合疗法治疗癌症提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Combination therapy involving HSP90 inhibitors for combating cancer: an overview of clinical and preclinical progress

The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.

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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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