Sun Wanyu, Lv Shuting, Li Hong, Cui Wei, Wang Lihui
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
Genes (Basel). 2018 Dec 14;9(12):633. doi: 10.3390/genes9120633.
In the nucleus of each cell, the DNA is wrapped around histone octamers, forming the so-called "nucleosomal core particles". The histones undergo various modifications that influence chromatin structure and function, including methylation, acetylation, ubiquitination, phosphorylation, and SUMOylation. These modifications, known as epigenetic modifications (defined as heritable molecular determinants of phenotype that are independent of the DNA sequence), result in alterations of gene expression and changes in cell behavior. Recent work has shown that epigenetic drugs targeting histone deacetylation or methylation modulate the immune response and overcome acquired resistance to immunotherapy. A number of combination therapies involving immunotherapy and epigenetic drugs, which target histone deacetylation or methylation, are currently under various clinical/pre-clinical investigations and have shown promising anticancer efficacy. These combination therapies may provide a new strategy for achieving sustained anticancer efficacy and overcoming resistance.
在每个细胞的细胞核中，DNA缠绕在组蛋白八聚体周围，形成所谓的“核小体核心颗粒”。组蛋白会经历各种修饰，这些修饰会影响染色质的结构和功能，包括甲基化、乙酰化、泛素化、磷酸化和SUMO化。这些修饰被称为表观遗传修饰（定义为独立于DNA序列的可遗传的表型分子决定因素），会导致基因表达的改变和细胞行为的变化。最近的研究表明，靶向组蛋白去乙酰化或甲基化的表观遗传药物可调节免疫反应并克服对免疫疗法的获得性耐药。目前，一些涉及免疫疗法和靶向组蛋白去乙酰化或甲基化的表观遗传药物的联合疗法正处于各种临床/临床前研究阶段，并已显示出有前景的抗癌疗效。这些联合疗法可能为实现持续的抗癌疗效和克服耐药性提供一种新策略。
