Research progress of BRD4 in head and neck squamous cell carcinoma: Therapeutic application of novel strategies and mechanisms

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2024-09-19 DOI:10.1016/j.bmc.2024.117929

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Abstract

Bromodomain-containing protein 4 (BRD4) belongs to the bromodomain and extra-terminal domain (BET) protein family, which plays a crucial role in recognizing acetylated lysine residues in chromatin. The abnormal expression of BRD4 contributes to the development of various human malignant tumors, including head and neck squamous cell carcinoma (HNSCC). Recent studies have shown that BRD4 inhibition can effectively prevent the proliferation and growth of HNSCC. However, the specific role and mechanism of BRD4 in HNSCC are not yet fully clarified. This article will briefly summarize the critical role of BRD4 in the pathogenesis of HNSCC and discuss the potential clinical applications of targeting BRD4 in HNSCC therapy. We further inquiry the challenges and opportunities for HNSCC therapies based on BRD4 inhibition, including BRD4 inhibitor combination with conventional chemotherapy, radiotherapy, and immunotherapy, as well as new strategies of BRD4-targeting drugs and BRD4 proteolysis-targeting chimeras (PROTACs). Moreover, we will also offer outlook on the associated challenges and future directions of targeting BRD4 for the treatment of patients with HNSCC.

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BRD4 在头颈部鳞状细胞癌中的研究进展：新策略和新机制的治疗应用

含溴结构域蛋白4（BRD4）属于溴结构域和末端外结构域（BET）蛋白家族，在识别染色质中的乙酰化赖氨酸残基方面起着至关重要的作用。BRD4的异常表达会导致包括头颈部鳞状细胞癌（HNSCC）在内的多种人类恶性肿瘤的发生。最近的研究表明，抑制 BRD4 可以有效阻止 HNSCC 的增殖和生长。然而，BRD4在HNSCC中的具体作用和机制尚未完全明确。本文将简要总结BRD4在HNSCC发病机制中的关键作用，并探讨靶向BRD4在HNSCC治疗中的潜在临床应用。我们将进一步探讨基于BRD4抑制的HNSCC疗法所面临的挑战和机遇，包括BRD4抑制剂与传统化疗、放疗和免疫疗法的联合应用，以及BRD4靶向药物和BRD4蛋白水解靶向嵌合体（PROTACs）的新策略。此外，我们还将展望靶向 BRD4 治疗 HNSCC 患者的相关挑战和未来方向。

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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来源期刊

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.