癌症的靶向基因-病毒治疗新进展及抗癌策略  

A Mini-review of Targeting Gene-Virotherapy of Cancer

作　　者：刘新垣[1,2] 顾锦法 

机构地区：[1]浙江理工大学生命科学院,新元医学与生物技术研究所,浙江杭州310018 [2]中科院上海生命科学院,生物化学与细胞生物学研究所,上海200031

出　　处：《癌症》2006年第10期1320-1322,共3页Chinese Journal of Cancer

基　　金：国家"973"项目(No.2004CB518804);"863"国家高技术研究发展计划(No.2002AA216021);国家自然科学基金(No.30120160823)~~

摘　　要：我们创导的“靶向基因-病毒治疗”又有新进展,即癌症的靶向双基因-病毒治疗,能将小鼠移植性肿瘤全部杀灭,研究结果发表于Hepatology及CancerResearch(Highlightpaper)等杂志。在得到好的抗癌作用后,我们着重研究其安全性,故本文又介绍一种独特的癌症双靶向病毒-双基因治疗,其特点是利用癌症特异性启动子调控其特异性抑制基因,如用甲胎蛋白(!-fetoprotein,AFP)调控肝癌特异性抑癌基因LFIRE或HCCS1等,并在此基础上再加一个癌症特异性启动子如hTERT控制腺病毒E1A,构成癌症的双靶向病毒-基因治疗药物,即hTERT-E1A-AFP-E1B-HCCS1(或LFIRE),然后再与一个杀伤功能很强的hTERT-E1A-AFP-E1B-IL-24联合作用,构成癌症的双靶向病毒-双基因治疗。双基因有很好的杀伤性,双靶向有很好的安全性,因此,成为目前开发前景良好的抗癌药物。此外,本文还介绍了一种新型干扰素,它也有可能成为理想的抗癌药物。New progress has been made on the project ＂targeting genevirotherapy of cancer＂ proposed by us, which is ＂targeting dual genevirotherapy of cancer＂. By the use of two genes, all the xenograft tumors in nude mice could be completely eliminated. The researches have been published in international journals, such as Hepatology and Cancer Research （a highlight paper）. In this study, a further superior strategy-＂double targeting virus-dual gene therapy＂ was introduced, This strategy was specialized by the use of tumor specific promoter to control the tumor specific suppressor gene, such as α-fetoprotein （AFP）, which controls hepatoma specific suppressor gene LFIRE or HCCSl. In addition, a second tumor specific promoter, such as hTERT or survivin was used to control E1A or E1B in the construct, as hTERT-E1A-AFP-E1B-HCCS1 or LFIRE, a double tumor specific promoter controlling hepatoma specific LFIRE or HCCSl gene. By the combined use of this construct with a very strong antitumor construct, such as hTERT-E1A-AFP-E1B-IL-24, a strategy with both excellent tumor killing effect and excellent safety with very little damage to normal cells was obtained. Therefore, double targeting virus-dual gene therapy might be one of the most potential strategies for cancer treatment. Furthermore, a new type of interferon was also introduced, which might be an ideal antitumor drug.

关 键 词：肿瘤/基因治疗 靶向治疗 双肿瘤特异性启动子载体 肿瘤特异性抑癌 基因 干扰素 

分 类 号：R730.5[医药卫生—肿瘤]