Verma Mukesh, Banerjee Hirendra Nath
Methods and Technologies Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, MD, 20852, USA.
Methods Mol Biol. 2015;1238:469-85. doi: 10.1007/978-1-4939-1804-1_24.
Traditional treatments for cancer include chemotherapy, radiation therapy, and surgery. Recently, epigenetic inhibitors have been found to be very effective in cancer treatment. Epigenetic changes such as DNA methylation, histone deacetylation, and microRNA (miRNA) expression are capable of silencing the expression of tumor suppressor genes and inducing oncogenes, leading to clonal proliferation of tumor cells. Methyltransferase inhibitors and histone deacetylase inhibitors have attracted the attention of researchers and clinicians because they provide an alternative therapeutic regime in some diseases, including cancer.Epigenetic changes are characterized by altered gene expression without any changes in the nucleotide sequences of DNA. In addition, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. 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, several epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. Their mechanisms of action and potential in treating cancer are described in this article.
癌症的传统治疗方法包括化疗、放疗和手术。最近,人们发现表观遗传抑制剂在癌症治疗中非常有效。DNA甲基化、组蛋白去乙酰化和微小RNA(miRNA)表达等表观遗传变化能够使肿瘤抑制基因的表达沉默并诱导癌基因,从而导致肿瘤细胞的克隆增殖。甲基转移酶抑制剂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,因为它们在包括癌症在内的一些疾病中提供了一种替代治疗方案。表观遗传变化的特征是基因表达改变而DNA的核苷酸序列没有任何变化。此外,表观遗传变化是动态的,可以被表观遗传抑制剂逆转。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。表观遗传抑制剂可以单独使用或与其他治疗药物联合使用。迄今为止,几种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。本文描述了它们的作用机制和治疗癌症的潜力。