肺癌精准医学中的表观遗传学：从实验室到临床——一篇叙述性综述
Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.
作者
作者单位
- Department of Thoracic Surgery and Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
摘要
中文
肺癌是全球最常见的恶性肿瘤之一。尽管早期检测和标准治疗在降低总体死亡率方面取得了进展，但推进精准肺癌护理仍迫切需要优化的联合方案、可靠的生物标志物和个体化策略。以DNA甲基化和组蛋白赖氨酸去乙酰化酶（HDAC）抑制剂为代表的表观遗传靶向药物已显示出令人鼓舞的抗肿瘤效果，美国食品药品监督管理局（FDA）批准的EZH2抑制剂他泽司他（Tazemetostat）进一步验证了表观遗传治疗在多种肿瘤中的转化价值。本叙述性综述系统总结了肺癌中的表观遗传改变和相应的靶向抑制剂，并阐明了表观遗传工具在诊断生物标志物开发和分层精准治疗中的临床前景。我们检索了PubMed和Web of Science核心合集，检索时间从数据库建立至2026年1月31日，关键词涵盖肺癌、DNA甲基化、组蛋白修饰和表观遗传靶向治疗。仅保留英文全文原创文章和综述。本综述系统描述了肺癌中异常的表观遗传特征，包括DNA甲基化、组蛋白甲基化以及最近发现的组蛋白乳酰化，同时详细介绍了适用于诊断和靶向治疗的表观遗传生物标志物。我们进一步总结了KMT/KDM、HDAC、EZH2和LSD1抑制剂在不同肺癌亚型中的亚型特异性研究进展，其核心功能包括抑制肿瘤增殖、调节神经内分泌表型转换、逆转治疗耐药和增强抗肿瘤免疫反应。失调的表观遗传修饰是肺癌进展的核心驱动因素，各种表观遗传小分子抑制剂在肺癌精准治疗中具有广泛的潜在应用。将表观遗传药物与免疫治疗或化疗相结合的联合方案可以增强抗肿瘤反应，但亚型异质性和某些靶向药物疗效不佳仍然是主要障碍。本文总结的临床前和临床表观遗传学证据为开发新型诊断生物标志物和针对肺癌的个体化分层治疗策略提供了坚实的理论支持。
English
Lung cancer ranks among the most prevalent malignancies globally. Despite progress in early detection and standard therapies lowering overall mortality, there remains an urgent demand for optimized combinatorial regimens, reliable biomarkers and individualized strategies to advance precision lung cancer care. Epigenetic-targeted agents, represented by DNA methylation and histone lysine deacetylase (HDAC) inhibitors, have exhibited encouraging anti-tumor effects, and the Food and Drug Administration (FDA)-approved EZH2 inhibitor tazemetostat has further validated the translational value of epigenetic therapy across multiple tumors. This narrative review systematically summarizes epigenetic alterations and corresponding targeted inhibitors in lung cancer, and clarifies the clinical prospects of epigenetic tools for diagnostic biomarker development and stratified precision treatment. We searched PubMed and Web of Science Core Collection from database inception to January 31, 2026 with keywords covering lung cancer, DNA methylation, histone modification and epigenetic targeted therapy. Only full-text English original articles and reviews were retained. This review systematically characterizes aberrant epigenetic signatures in lung cancer, encompassing DNA methylation, histone methylation, and the recently discovered histone lactylation, while detailing epigenetic biomarkers applicable to diagnosis and targeted therapy. We further summarize subtype-specific research advances of KMT/KDM, HDAC, EZH2 and LSD1 inhibitors in distinct lung cancer subtypes, with core functions including suppressing tumor proliferation, modulating neuroendocrine phenotypic transition, reversing therapeutic resistance, and amplifying anti-tumor immune responses. Dysregulated epigenetic modifications serve as core drivers of lung cancer progression, and various epigenetic small-molecule inhibitors possess broad application potential for lung cancer precision treatment. Combined regimens integrating epigenetic agents with immunotherapy or chemotherapy can strengthen anti-tumor responses, yet subtype heterogeneity and unsatisfactory clinical efficacy of some targeted drugs remain major obstacles. The accumulated preclinical and clinical epigenetic evidence summarized herein provides solid theoretical support for developing novel diagnostic biomarkers and individualized stratified therapeutic strategies against lung cancer.
分类与指标
- 研究类型
- 综述Meta
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 3.4
- 新锐分区
- 3区