Peedicayil Jacob
Department of Pharmacology & Clinical Pharmacology, Christian Medical College, Vellore, India.
Indian J Med Res. 2006 Jan;123(1):17-24.
Epigenetics, heritable changes in gene expression that do not involve changes in DNA sequence, is known to be involved in disease. Two important epigenetic changes that are known to contribute to disease are abnormal methylation patterns of DNA and modifications of histones in chromatin. This review describes a new development in pharmacology, epigenetic therapy, which attempts to correct these changes. At present two groups of drugs are being developed. One inhibits DNA methyltransferases (DNMTs) resulting in the inhibition of DNA methylation. This group of drugs may prove to be useful in the treatment of cancer where hypermethylation of tumour suppressor genes is known to lead to silencing of these genes. The other group of drugs inhibits histone deacetylases (HDACs) resulting in the accumulation of acetylated histones which are thought to mediate the anticancer effects of these drugs. Both these drug groups have shown promising results in drug trials for the treatment of cancer. Since epigenetic changes are thought to underlie a wide range of diseases, the scope of epigenetic therapy is likely to expand.
表观遗传学是指基因表达的可遗传变化，这种变化不涉及DNA序列的改变，已知其与疾病有关。已知导致疾病的两种重要表观遗传变化是DNA的异常甲基化模式和染色质中组蛋白的修饰。本综述描述了药理学领域的一项新进展——表观遗传疗法，该疗法试图纠正这些变化。目前正在研发两类药物。一类抑制DNA甲基转移酶（DNMTs），从而抑制DNA甲基化。已知肿瘤抑制基因的高甲基化会导致这些基因沉默，这类药物可能在癌症治疗中有用。另一类药物抑制组蛋白脱乙酰酶（HDACs），导致乙酰化组蛋白积累，人们认为这些乙酰化组蛋白介导了这些药物的抗癌作用。这两类药物在癌症治疗的药物试验中均显示出了有前景的结果。由于表观遗传变化被认为是多种疾病的基础，表观遗传疗法的应用范围可能会扩大。
