Hematology/Oncology Fellowship Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncology (Williston Park). 2011 Mar;25(3):220-6, 228.
Epigenetics is a rapidly expanding field that focuses on stable changes in gene expression that are not accompanied by changes in DNA sequence and that are mediated primarily by DNA methylation and histone modifications. Disruption of the epigenome is a fundamental mechanism in cancer, and several epigenetic drugs that have proved to prolong survival and to be less toxic than conventional chemotherapy were recently approved by the FDA for cancer treatment. These include azacitidine (Vidaza), decitabine (Dacogen), vorinostat (Zolinza), and romidepsin (Istodax). Promising results of combination clinical trials with DNA methylation inhibitors and histone deacetylase inhibitors have recently been reported, and data are emerging that describe molecular determinants of clinical responses. Despite significant advances, challenges remain, including a lack of predictive markers, unclear mechanisms of response and resistance, and rare responses in solid tumors. Preclinical studies are ongoing with novel classes of agents that target various components of the epigenetic machinery. In this review, we focus on recent clinical and translational data in the epigenetics field that have potential in cancer therapy.
表观遗传学是一个快速发展的领域，主要关注基因表达的稳定变化，这些变化不伴随 DNA 序列的改变，主要由 DNA 甲基化和组蛋白修饰介导。表观基因组的破坏是癌症的一个基本机制，最近 FDA 批准了几种已被证明能延长生存期且比传统化疗毒性更小的表观遗传学药物用于癌症治疗。这些药物包括阿扎胞苷（Vidaza）、地西他滨（Dacogen）、伏立诺他（Zolinza）和罗米地辛（Istodax）。最近有报道称，联合使用 DNA 甲基化抑制剂和组蛋白去乙酰化酶抑制剂的临床试验取得了有希望的结果，并且有数据表明描述了临床反应的分子决定因素。尽管取得了重大进展，但仍存在挑战，包括缺乏预测标志物、反应和耐药机制不明确以及实体瘤反应罕见。正在进行针对表观遗传学机制中各种成分的新型药物的临床前研究。在这篇综述中，我们重点介绍了癌症治疗中具有潜力的表观遗传学领域的最新临床和转化数据。
