选择性组蛋白去乙酰化酶抑制剂抗肿瘤作用的研究进展

Progress in the Research of Selective Histone Deacetylase Inhibitors

关键词:  

Key words:  HDAC inhibitor  selective  tumor therapy  mechanism  clinical application

摘要:

核心组蛋白的乙酰化和去乙酰化在调节基因表达方面起着重要作用，与肿瘤的发生密切相关。目的 讨论单一组蛋白去乙酰化酶(histone deacetylase，HDAC)亚型作为抗肿瘤药物靶点的可行性以及他们在癌症中的致癌能力。方法 大量的组蛋白去乙酰化酶抑制剂已被研发，并且在临床实验中进行评估，表现出了较好的抗肿瘤活性。结果 这些化合物大部分都不具有选择性，I期临床中表现出了很多方面的副作用。结论 这个领域最值得研究的方向就是设计出选择性的抑制剂，仅仅作用于肿瘤细胞，而对正常细胞不造成影响。

Abstract:

It is very important for acetylation and deacetylation of chromatin histone to regulate the gene transcription by histone deacetylase, which is closely related with tumor. OBJECTIVE The aim of this review is to discuss the possibility of a single HDAC family member as drug targets in cancer and their oncogenic potential in cancer disease. METHODS The first HDAC inhibitors have been evaluated in clinical trials and show activity against several cancer diseases. RESULTS However, these compounds don’t act selectively against most parts of HDAC family, and they show a lot of side effects in clinical phase I. CONCLUSION So the question in this field is to find the cancer relevant HDAC family members in the certain tumor and to design selective HDAC inhibitors, which target cancer cells but leave out normal cells.