The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy

IF 7.6 Q1 ONCOLOGY Journal of the National Cancer Center Pub Date : 2022-12-01 DOI:10.1016/j.jncc.2022.09.002

Yunkai Yang , Min Zhang , Yan Wang

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引用次数: 8

Abstract

Histone modifications are key factors in chromatin packaging, and are responsible for gene regulation during cell fate determination and development. Abnormal alterations in histone modifications potentially affect the stability of the genome and disrupt gene expression patterns, leading to many diseases, including cancer. In recent years, mounting evidence has shown that various histone modifications altered by aberrantly expressed modifier enzymes contribute to tumor development and metastasis through the induction of epigenetic, transcriptional, and phenotypic changes. In this review, we will discuss the existing histone modifications, both well-studied and rare ones, and their roles in solid tumors and hematopoietic cancers, to identify the molecular pathways involved and investigate targeted therapeutic drugs to reorganize the chromatin and enhance cancer treatment efficiency. Finally, clinical inhibitors of histone modifications are summarized to better understand the developmental stage of cancer therapy in using these drugs to inhibit the histone modification enzymes.

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组蛋白修饰在肿瘤发生中的作用以及相关抑制剂在癌症治疗中的作用

组蛋白修饰是染色质包装的关键因素，在细胞命运决定和发育过程中负责基因调控。组蛋白修饰的异常改变可能会影响基因组的稳定性，破坏基因表达模式，导致包括癌症在内的许多疾病。近年来，越来越多的证据表明，由异常表达的修饰酶改变的各种组蛋白修饰通过诱导表观遗传、转录和表型变化参与肿瘤的发展和转移。在这篇综述中，我们将讨论现有的组蛋白修饰，包括研究充分的和罕见的修饰，以及它们在实体瘤和造血癌中的作用，以确定所涉及的分子途径，并研究靶向治疗药物来重组染色质，提高癌症治疗效率。最后，总结了组蛋白修饰的临床抑制剂，以便更好地了解使用这些药物抑制组蛋白修饰酶治疗癌症的发展阶段。

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