转录靶向性溶瘤腺病毒治疗肺癌研究的现状与思考  

Current situation and thinking of transcriptional targeted oncolytic adenovirus in the treatment of lung cancer

作　　者：时辉[1] 车国卫[1] 

机构地区：[1]四川大学华西医院胸外科,四川成都610041

出　　处：《中华肿瘤防治杂志》2011年第13期1049-1053,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30872547)

摘　　要：目的:总结分析国内外应用转录靶向性溶瘤腺病毒治疗肺癌的进展和面临的困难。方法:以"腺病毒、肺癌、启动子"为关键词,检索CNKI及PubMed数据库,年限为2000-2010,相关文献72篇,其中中文文献16篇,英文56篇。纳入标准:1)以腺病毒为载体治疗肺癌;2)用肺癌基因启动子取代腺病毒复制必须基因启动子。根据纳入标准分析23篇文献。结果:转录靶向性溶瘤腺病毒是应用肿瘤特异性启动子调控腺病毒复制必须基因的表达,使腺病毒只在特定的肿瘤细胞中复制、扩增,从而能最大程度地靶向杀伤肿瘤细胞,而不杀伤正常细胞。可应用于肺癌的肿瘤特异性启动子有10余种,用这些特异性启动子取代腺病毒复制起始基因启动子后,腺病毒复制必须基因序列因受其特异性调控,只在肺癌细胞中复制、扩增,从而最大程度地靶向杀伤肺癌细胞,不杀伤正常细胞;同时,腺病毒载体的优越性在于其能保证启动子和治疗基因安全、稳定、高效地在肺癌组织中表达。这使得靶向性溶瘤腺病毒在肺癌治疗研究中取得了显著进展,但这些研究多集中于体外实验及动物体内实验,临床应用尚面临诸多困难。结论:转录靶向性溶瘤腺病毒为肺癌的治疗提供了新思路,如能突破目前研究中所面临的种种困难,进一步全面、深入研究肺癌的发病机制,探寻特异性更强的肺癌启动子,增强溶瘤腺病毒的靶向性,降低毒副反应,可望广泛应用于临床。OBJECTIVE：To review current advances and difficulties of transcriptional targeted oncolytic adenovirus in the treatment of lung cancer.METHODS： A total of 72 papers were searched with adenovirus,lung cancer and promoter as the key words in CNKI and PubMed database from 2000 to 2010,16 papers of literature in Chinese and 56 in English.The selection standards for the date related： 1） Adenovirus therapy in lung cancer;2） Promoter therapy in lung cancer.According to the above standards,23 were finally selected and analyzed.RESULTS：Over 10 kinds of tumour specific promoters applided in the treatment of lung cancer have been discovered.They can be utilized to control the expression of early adenovirus genes essential for replication.The specificity of the lung cancer promoters and the safety,stability,efficiency of the adenovirus vector make transcriptional targeted oncolytic adenovirus selectively replicate,spread and maximally destroy lung cancer cells without killing normal cells.It has made great progress in preclinical models,though,there are a variety of diffigulties in the practice of cilinical trials.CONCLUSIONS： Transcriptional targeted oncolytic adenovirus have enormous potential for the treatment lung cancer.The translation of this novel therapeutic modality from the preclinical setting to the clinic will be driven by comprehensively studying the pathogenesis of lung cancer,exploring more specific lung cancer promoters and enhancing the safety of adenovirus vectors.

关 键 词：肺肿瘤 基因治疗 腺病毒科 综述文献 

分 类 号：R734.2[医药卫生—肿瘤]