Hepatitis B virus–induced hepatocellular carcinoma: HBx-associated epigenetic mechanisms and therapeutic opportunities

IF 6.4 3区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cancer gene therapy Pub Date : 2026-06-13 DOI:10.1038/s41417-026-01051-6

Atahar Husein, Azfar Jamal, Mohammad Azhar Kamal, Yaser E. Alqurashi, Esam S. Al-Malki, Mohammed M. Naiyer, Syed Arif Hussain, Mohiuddin Khan Warsi

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Abstract

Chronic hepatitis B virus (HBV) infection is a major etiological factor in the development of hepatocellular carcinoma (HCC), a cancer that causes a large number of cancer-related deaths around the world. Although antiviral treatments are effective, the risk of HCC remains because studies using advanced sequencing have shown that liver cells still carry integrated viral DNA, experience ongoing inflammation, and undergo lasting changes in epigenetic regulation. HBV maintains its genome in liver cells as a chromatin-like cccDNA structure, and with the help of the HBx protein, it manipulates the cell’s chromatin machinery to support viral gene expression and disrupt normal control of enhancers, DNA methylation, and Polycomb regulation. These alterations enhance transcriptional plasticity and, in the context of chronic liver injury and additional somatic mutations, may contribute to malignant transformation. This review highlights recent mechanistic studies that have suggested a pathway linking HBV persistence to chromatin dysfunction. Further, it outlines an emerging therapeutic opportunity with chromatin-directed drugs, as well as rational combinations of these drugs with immunotherapy for HBV-related HCC.

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乙型肝炎病毒诱导的肝细胞癌：hbx相关的表观遗传机制和治疗机会

慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）发展的主要病因，HCC是一种导致全球大量癌症相关死亡的癌症。尽管抗病毒治疗是有效的，但HCC的风险仍然存在，因为使用先进测序的研究表明，肝细胞仍然携带整合的病毒DNA，经历持续的炎症，并经历持久的表观遗传调控变化。HBV在肝细胞中以染色质样cccDNA结构维持其基因组，在HBx蛋白的帮助下，它操纵细胞的染色质机制来支持病毒基因表达，并破坏对增强子、DNA甲基化和Polycomb调控的正常控制。这些改变增强了转录的可塑性，在慢性肝损伤和额外的体细胞突变的情况下，可能有助于恶性转化。这篇综述强调了最近的机制研究，这些研究表明HBV持久性与染色质功能障碍之间存在联系。此外，它概述了染色质导向药物的新兴治疗机会，以及这些药物与hbv相关HCC免疫治疗的合理组合。

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

Cancer gene therapy 医学-生物工程与应用微生物

CiteScore

10.20

自引率

0.00%

发文量

150

审稿时长

4-8 weeks

期刊介绍： Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.