Research progress of multi-target HDAC inhibitors blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway in the treatment of cancer

IF 3.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2024-07-02 DOI:10.1016/j.bmc.2024.117827
Shuting Jia , Yuye Jia , Sufang Liang , Liqiang Wu
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Abstract

Histone deacetylase inhibitors (HDACis) show beneficial effects on different hematological malignancy subtypes. However, their impacts on treating solid tumors are still limited due to diverse resistance mechanisms. Recent studies have found that the feedback activation of BRD4-LIFR-JAK1-STAT3 pathway after HDACi incubation is a vital mechanism inducing resistance of specific solid tumor cells to HDACis. This review summarizes the recent development of multi-target HDACis that can concurrently block BRD4-LIFR-JAK1-STAT3 pathway. Moreover, our findings hope to shed novel lights on developing novel multi-target HDACis with reduced BRD4-LIFR-JAK1-STAT3-mediated drug resistance in some tumors.

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多靶点 HDAC 抑制剂阻断 BRD4-LIFR-JAK1-STAT3 信号通路治疗癌症的研究进展。
组蛋白去乙酰化酶抑制剂(HDACis)对不同的血液恶性肿瘤亚型都有良好的疗效。然而,由于耐药机制的多样性,它们对治疗实体瘤的影响仍然有限。最近的研究发现,HDACi孵育后BRD4-LIFR-JAK1-STAT3通路的反馈激活是诱导特定实体瘤细胞对HDACis产生耐药性的重要机制。本综述总结了近年来可同时阻断BRD4-LIFR-JAK1-STAT3通路的多靶点HDACis的发展情况。此外,我们的研究结果有望为开发新型多靶点HDACis提供新的启示,减少某些肿瘤中BRD4-LIFR-JAK1-STAT3介导的耐药性。
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来源期刊
Bioorganic & Medicinal Chemistry
Bioorganic & Medicinal Chemistry 医学-生化与分子生物学
CiteScore
6.80
自引率
2.90%
发文量
413
审稿时长
17 days
期刊介绍: Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
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