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胃肠道恶性肿瘤中的表观遗传学和治疗靶点。

Epigenetics and therapeutic targets in gastrointestinal malignancies.

机构信息

Department of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA.

Dr L.V. Prasad Diagnostics and Research Laboratory, Khairtabad, Hyderabad 500004, India.

出版信息

Drug Discov Today. 2021 Oct;26(10):2303-2314. doi: 10.1016/j.drudis.2021.04.013. Epub 2021 Apr 22.

Abstract

Gastrointestinal (GI) malignancies account for substantial mortality and morbidity worldwide. They are generally promoted by dysregulated signal transduction and epigenetic pathways, which are controlled by specific enzymes. Recent studies demonstrated that histone deacetylases (HDACs) together with DNA methyltransferases (DNMTs) have crucial roles in the signal transduction/epigenetic pathways in GI regulation. In this review, we discuss various enzyme targets and their functional mechanisms responsible for the regulatory processes of GI malignancies. We also discuss the epigenetic therapeutic targets that are mainly facilitated by DNMT and HDAC inhibitors, which have functional consequences and clinical outcomes for GI malignancies.

摘要

胃肠道(GI)恶性肿瘤在全球范围内导致了大量的死亡和发病。它们通常是由失调的信号转导和表观遗传途径引起的,这些途径受特定酶的控制。最近的研究表明,组蛋白去乙酰化酶(HDACs)与 DNA 甲基转移酶(DNMTs)一起在 GI 调节的信号转导/表观遗传途径中起着至关重要的作用。在这篇综述中,我们讨论了各种酶靶标及其功能机制,这些酶靶标负责 GI 恶性肿瘤的调节过程。我们还讨论了主要由 DNMT 和 HDAC 抑制剂介导的表观遗传治疗靶点,这些靶点对 GI 恶性肿瘤具有功能后果和临床结果。

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