组蛋白去乙酰化酶抑制剂(HDACi)逆转非小细胞肺癌耐药性的新进展  

Histone deacetylase inhibitors(HDACi)overcoming chemotherapy,targeted-therapy and immunotherapy resistance in NSCLC

作　　者：孟萌[1] 李红玲 李凤丽[1] Meng Meng;Li Hongling;Li Fengli(The First Affiliated Hospital of Tianjin University of TCM,Tianjin 300193;Lingyuan central hospital,Liaoning 122500)

机构地区：[1]天津中医药大学第一附属医院,天津300193 [2]辽宁省凌源市中心医院,辽宁122500

出　　处：《天津药学》2020年第2期48-53,共6页Tianjin Pharmacy

基　　金：国家“重大新药创制”科技重大专项项目(No.2010ZX09102-201)。

摘　　要：组蛋白乙酰化途径在多种类型肿瘤的发生、发展及转移等恶性表型中发挥重要作用,并受组蛋白乙酰基转移酶(histone acetyltransferase,HAT)和组蛋白去乙酰化酶(histone deacetylase,HDAC)两类酶调节。组蛋白去乙酰化酶抑制剂(HDAC inhibitors,HDACi)通过改变细胞内组蛋白乙酰化程度影响染色质空间结构、染色体重塑,从而抑制目的基因转录,对肿瘤发生、耐药起到关键作用。近年来研究表明,HDCAi能够逆转多种类型非小细胞肺癌获得性耐药,包括逆转肺癌细胞对常规铂类化疗、精准分子靶向治疗及肿瘤免疫检查点治疗的耐药性。因此,本文就组蛋白乙酰化酶的结构与分类、组蛋白去乙酰化酶抑制剂及基于HDACi克服非小细胞肺癌获得性耐药的机制与策略予以综述。Objective:The histone acetylation pathway plays a crucial role in the multiple malignant processes of tumorigenesis and metastasis,and could be manipulated by histone acetyltransferase(HAT)and histone deacetylase(HDAC).HDAC inhibitors(HDACi)affect the spatial structure of chromatin via changing the degree of acetylation of histones,and then remodeling chromosome,thereby inhibiting the transcription of the target genes and playing a key role in tumorigenesis and drug resistance.Recently,increasing evidences have shown that HDCAi can reverse the many types of acquired drug resistance in non-small cell lung cancer(NSCLC),including reversing the resistance of lung cancer cells to conventional platinum-based chemotherapy,precision targeted therapy,and cancer immune checkpoint therapy.Therefore,we summarized the structure and classification of HDAC,HDAC inhibitors,and mechanisms and strategies based on HDACi to overcome various acquired drug resistance in NSCLC.

关 键 词：非小细胞肺癌 组蛋白去乙酰化酶 获得性耐药 靶向治疗 免疫治疗 

分 类 号：R979.1[医药卫生—药品]