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肝癌分子理解、早期检测和靶向治疗方面的进展与挑战

英文原题:Advances and challenges in molecular understanding, early detection, and targeted treatment of liver cancer.

查看英文原题

Advances and challenges in molecular understanding, early detection, and targeted treatment of liver cancer.

PubMed 2025/01/27(内容时间) World J Hepatol Q2 · IF 3.4(JCR 2025)

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中文摘要

在这篇综述中,我们探讨了下一代测序在肝癌研究中的应用,强调其在现代肿瘤学中的潜力。肝癌,尤其是肝细胞癌,是由遗传、表观遗传和环境因素复杂相互作用驱动的。关键遗传改变,如 TERT、TP53 和 CTNNB1 的突变,以及 DNA 甲基化和组蛋白重塑等表观遗传修饰,会破坏调控通路并促进肿瘤发生。环境因素,包括病毒感染、饮酒以及非酒精性脂肪性肝病等代谢紊乱,会增强肝癌发生。肿瘤微环境在肝癌进展和治疗耐药中发挥关键作用,免疫细胞浸润、纤维化和血管生成支持癌细胞存活。免疫检查点抑制剂和CAR-T 细胞疗法的进展已显示出潜力,但肝癌中独特的免疫抑制环境带来了挑战。Wnt/β-catenin 等通路的失调凸显了靶向治疗策略的必要性。下一代测序正在加速识别遗传和表观遗传改变,从而实现更精确的诊断和个性化治疗方案。更深入地理解这些分子机制对于推进肝癌早期检测和开发有效疗法至关重要。

展开英文摘要原文

In this review, we explore the application of next-generation sequencing in liver cancer research, highlighting its potential in modern oncology. Liver cancer, particularly hepatocellular carcinoma, is driven by a complex interplay of genetic, epigenetic, and environmental factors. Key genetic alterations, such as mutations in TERT , TP53 , and CTNNB1 , alongside epigenetic modifications such as DNA methylation and histone remodeling, disrupt regulatory pathways and promote tumorigenesis. Environmental factors, including viral infections, alcohol consumption, and metabolic disorders such as nonalcoholic fatty liver disease, enhance hepatocarcinogenesis.

The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance, with immune cell infiltration, fibrosis, and angiogenesis supporting cancer cell survival. Advances in immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies have shown potential, but the unique immunosuppressive milieu in liver cancer presents challenges.

Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies. Next-generation sequencing is accelerating the identification of genetic and epigenetic alterations, enabling more precise diagnosis and personalized treatment plans. A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.

论文信息

作者
Shi J、Zhu X、Yang JB
第一作者单位
Department of Research and Development, Ruibiotech Company Limited, Beijing 100101, China.China
通讯作者单位
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, Guangdong Province, China. 1806389316@pku.edu.cn.China
文献类型
综述
期刊
World journal of hepatology2025 Jan 27
原文标识
PubMed 39871899 · DOI 10.4254/wjh.v17.i1.102273