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HDAC 抑制剂在癌症治疗中的潜在作用:口腔鳞状细胞癌的研究进展。

Potential role of HDAC inhibitors in cancer therapy: insights into oral squamous cell carcinoma.

机构信息

Dentistry Biomedical Research Department, University of Seville, 41009 Seville, Spain.

出版信息

Oral Oncol. 2010 May;46(5):323-9. doi: 10.1016/j.oraloncology.2010.01.009. Epub 2010 Mar 7.

Abstract

Histone deacetylases (HDACs) are enzymes that are involved in the remodeling of chromatin and play a key role in the epigenetic regulation of gene expression. In addition, the activity of non-histone proteins can be regulated through HDAC-mediated hypoacetylation. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anti-cancer activities in preclinical studies. Many researchers have highlighted the need to determine specific HDAC isotypes related to different tumor types in order to develop selective drugs for specific isoforms and avoid side effects. We summarize recent advances in the understanding of the molecular events that underlie the epigenetic changes in different tissue carcinomas, focusing on oral squamous carcinoma. The role of epigenetics in oral squamous cancer remains poorly understood, and further descriptive studies of specific HDAC member alterations are required to form the basis for future clinical trials.

摘要

组蛋白去乙酰化酶(HDACs)是参与染色质重塑的酶,在基因表达的表观遗传调控中起着关键作用。此外,非组蛋白的活性可以通过 HDAC 介导的低乙酰化来调节。近年来,抑制 HDACs 已成为一种潜在的策略,可以逆转与癌症相关的异常表观遗传变化,并且在临床前研究中发现几类 HDAC 抑制剂具有很强的特异性抗癌活性。许多研究人员强调,需要确定与不同肿瘤类型相关的特定 HDAC 同工型,以便为特定的同工型开发选择性药物并避免副作用。我们总结了近年来在理解不同组织癌中表观遗传变化的分子事件方面的进展,重点是口腔鳞状细胞癌。表观遗传学在口腔鳞状细胞癌中的作用仍知之甚少,需要进一步进行特定 HDAC 成员改变的描述性研究,为未来的临床试验奠定基础。

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