Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
Otolaryngology Unit, National Tumor Institute of Naples, G. Pascale, Italy.
Crit Rev Oncol Hematol. 2017 Mar;111:166-172. doi: 10.1016/j.critrevonc.2017.01.020. Epub 2017 Feb 4.
Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor suppressor gene promoters is responsible for their silencing and thus potentially sustain cancerogenesis. Similarly, histone deacetylation can lead to oncogene activation. mi-RNA are small (18-20 nucleotides) non-coding RNA fragments capable of inhibiting other m-RNA, ultimately altering the balance in oncogene and tumor suppressor gene expression. It has been shown that growth of several tumor types can be stimulated by epigenetic changes in various phases of cancerogenesis, and drugs able to interfere with these mechanisms can have a positive impact on tumor progression. As matter of fact, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. Recently, methyltransferase and histone deacetylase inhibitors have attracted the attention of researchers and clinicians as they potentially provide alternative therapeutic options in some cancers. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors work alone or in combination with other therapeutic agents. To date, a number of epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. In this review article we describe their mechanisms of action and potential in cancer treatment.
表观遗传变化被定义为不存在于 DNA 序列中的遗传修饰。基因表达在多个水平上受到调控，而不仅仅是对 DNA 修饰的反应。表观遗传控制的例子包括 DNA 甲基化、组蛋白去乙酰化和 miRNA 表达。几个肿瘤抑制基因启动子的甲基化负责它们的沉默，从而潜在地维持癌症的发生。同样，组蛋白去乙酰化可以导致癌基因的激活。miRNA 是小的（18-20 个核苷酸）非编码 RNA 片段，能够抑制其他 m-RNA，最终改变癌基因和肿瘤抑制基因表达的平衡。已经表明，几种肿瘤类型的生长可以通过癌症发生的各个阶段的表观遗传变化来刺激，并且能够干扰这些机制的药物可能对肿瘤进展产生积极影响。事实上，表观遗传变化是动态的，可以通过表观遗传抑制剂来逆转。最近，甲基转移酶和组蛋白去乙酰化酶抑制剂引起了研究人员和临床医生的关注，因为它们在某些癌症中可能提供替代治疗选择。抑制 DNA 甲基化或组蛋白去乙酰化的药物已被研究用于重新激活肿瘤抑制基因和抑制癌细胞生长。表观遗传抑制剂单独或与其他治疗剂联合使用。迄今为止，许多表观遗传抑制剂已被批准用于癌症治疗。表观遗传抑制剂领域的主要挑战是它们缺乏特异性。在这篇综述文章中，我们描述了它们的作用机制及其在癌症治疗中的潜力。
