Menzies Research Institute, Private Bag 23, University of Tasmania, Hobart, TAS 7001, Australia.
Curr Med Chem. 2010;17(13):1246-54. doi: 10.2174/092986710790936329.
Changes to the epigenetic information within a cell play a significant role in cancer development and progression. These epigenetic changes are important in establishing the aberrant gene expression patterns that are a feature of cancer cell biology. We are currently experiencing a rapid advance in our understanding of how epigenetic information is written and interpreted in the cell, and the enzymes involved in these processes have been recognised as prime targets for therapeutic intervention. Reagents that target these enzymes have the potential to inhibit or reverse epigenetic changes in cancer cells. Evidence suggests that the aberrant regulation of two gene silencing pathways; involving DNA methylation and histone methylation, play an important role in cancer development. Considerable effort is being exerted in the development of inhibitors of these pathways. However, complex functional interactions exist between the DNA and histone methylation pathways, and these interactions will need to be considered in the design of inhibitory molecules. This review details current research into agents developed as inhibitors of these epigenetic pathways, focusing on the types of epigenetic modifications being targeted, interactions between these modifications and the use of these inhibitory agents in cancer treatment.
细胞内表观遗传信息的改变在癌症的发生和发展中起着重要作用。这些表观遗传变化在建立癌症细胞生物学的特征性异常基因表达模式方面非常重要。我们目前正在迅速加深对细胞内如何编写和解释表观遗传信息的理解，并且这些过程中涉及的酶已被认为是治疗干预的主要靶点。针对这些酶的试剂有可能抑制或逆转癌细胞中的表观遗传变化。有证据表明，涉及 DNA 甲基化和组蛋白甲基化的两种基因沉默途径的异常调控在癌症的发展中起着重要作用。目前正在大力开发这些途径的抑制剂。然而，DNA 和组蛋白甲基化途径之间存在复杂的功能相互作用，在设计抑制分子时需要考虑这些相互作用。本文详细介绍了作为这些表观遗传途径抑制剂开发的试剂的当前研究，重点介绍了正在靶向的表观遗传修饰的类型、这些修饰之间的相互作用以及这些抑制性试剂在癌症治疗中的应用。
