HDAC抑制剂治疗血液恶性肿瘤新进展  

HDAC inhibitors-new situation in the treatment of hematologic malignancies

作　　者：张曼 刘爱春[1] ZHANG Man;LIU Aichun(Department of Hematology and Lymphatology,Harbin Medical University Affiliated Cancer Hospital,Heilongjiang Harbin 150081,China)

机构地区：[1]哈尔滨医科大学附属肿瘤医院血液淋巴科,黑龙江哈尔滨150081

出　　处：《现代肿瘤医学》2022年第14期2654-2658,共5页Journal of Modern Oncology

摘　　要：组蛋白乙酰化有利于转录因子与DNA位点结合,从而发挥基因表达作用。同时,乙酰化的组蛋白可以增加DNA对转录激活剂的活性,并减弱转录抑制因子的功能。组蛋白乙酰转移酶(HAT)和组蛋白去乙酰化酶(histone deacetylase,HDAC)是这一过程的重要媒介,HDAC的异常表达与许多血液系统恶性肿瘤息息相关,HDAC抑制可加快肿瘤细胞凋亡,所以小分子HDAC抑制剂(histone deacetylase inhibitor,HDACi)已被开发用于新型的抗癌药物,其中一些药物已进入临床研究阶段。目前基于HDAC抑制剂的治疗效果不一,但值得注意的是,血液系统恶性肿瘤对于HDAC抑制剂反应良好。然而,治疗耐药性仍然是一个关键问题。本篇综述强调了目前已获批准或正处于研究中的用于治疗血液系统恶性肿瘤的HDAC抑制剂的应用及治疗进展。Histone acetylation facilitates the binding of transcription factors to dna sites and thus exerts gene expression.At the same time,acetylated histones can increase DNA accessibility to transcriptional activators and counteract the function of transcriptional repressors.Histone acetyltransferases(HAT)and histone deacetylases(HDAC)are important mediators of this process.Abnormal expression of HDAC is closely related to many malignant tumors of the blood system.HDAC inhibition can accelerate tumor cell apoptosis.So,small molecule HDAC inhibitors have been developed for novel anticancer drugs,many of which have entered clinical trials.Currently,HDAC inhibitor-based treatment has a mixed effect,but it is worth noting that hematological malignancies respond well to HDAC inhibitors.However,treatment resistance remains a key issue.This review highlights the application and progress of hdac inhibitors currently approved or under investigation for the treatment of hematologic malignancies.

关 键 词：组蛋白去乙酰化酶抑制剂 血液系统恶性肿瘤 疗效 安全性 

分 类 号：R733.7[医药卫生—肿瘤]