癌症表观遗传学的临床实践

SCI 13 January 2022

Cancer epigenetics in clinical practice

（CA Cancer J Clin IF: 508.7)

1 Josep Carreras Leukaemia Research Institute, Badalona, Catalonia, Spain；2 Centro de Investigacion Biomedica en Red Cancer, Madrid, Spain； 3 Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain； 4 Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Catalonia, Spain 

Correspondence：Manel Esteller, Josep Carreras Leukaemia Research Institute (IJC), Carretera de Can Ruti, Camí de les Escoles s/n, 08916 Badalona, Catalonia, Spain. 

Abstract 摘要   

Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence, epigenetic alterations contribute to the acquisition of hallmark tumor capabilities by regulating gene expression programs that promote tumorigenesis. Shifts in DNA methylation and histone mark patterns, the two main epigenetic modifications, orchestrate tumor progression and metastasis. These cancer‐specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review sum- marizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation‐ based assays and epigenetic drugs already approved by the US Food and Drug Administration. 

癌症的发展是由影响基因组结构和功能的改变的积累所驱动的。遗传变化破坏了DNA序列，而表观遗传学的改变通过调节促进肿瘤发生的基因表达程序，有助于获得标志性的肿瘤能力。DNA甲基化和组蛋白标记模式的转变是两个主要的表观遗传学修饰，它协调了肿瘤的发展和转移。这些癌症特有的事件已被利用作为诊断、监测和治疗选择的有用工具，以帮助临床决策。此外，与基因变化的不可逆性相比，表观遗传修饰的可逆性使表观遗传机制成为药物开发的诱人目标。本综述总结了表观遗传生物标志物和表观遗传药物在临床上的最先进的应用，强调了基于DNA甲基化的商业化检测和已经被美国食品和药物管理局批准的表观遗传药物。