用于基因治疗的肿瘤内皮细胞的转录靶向
Transcriptional targeting of tumor endothelial cells for gene therapy.
作者信息
Dong Zhihong, Nör Jacques E
机构信息
Angiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
出版信息
Adv Drug Deliv Rev. 2009 Jul 2;61(7-8):542-53. doi: 10.1016/j.addr.2009.02.006. Epub 2009 Apr 23.
It is well known that angiogenesis plays a critical role in the pathobiology of tumors. Recent clinical trials have shown that inhibition of angiogenesis can be an effective therapeutic strategy for patients with cancer. However, one of the outstanding issues in anti-angiogenic treatment for cancer is the development of toxicities related to off-target effects of drugs. Transcriptional targeting of tumor endothelial cells involves the use of specific promoters for selective expression of therapeutic genes in the endothelial cells lining the blood vessels of tumors. Recently, several genes that are expressed specifically in tumor-associated endothelial cells have been identified and characterized. These discoveries have enhanced the prospectus of transcriptionally targeting tumor endothelial cells for cancer gene therapy. In this manuscript, we review the promoters, vectors, and therapeutic genes that have been used for transcriptional targeting of tumor endothelial cells, and discuss the prospects of such approaches for cancer gene therapy.
众所周知，血管生成在肿瘤的病理生物学中起着关键作用。最近的临床试验表明，抑制血管生成可能是癌症患者的一种有效治疗策略。然而，癌症抗血管生成治疗中一个突出的问题是与药物脱靶效应相关的毒性的产生。肿瘤内皮细胞的转录靶向涉及使用特定启动子在肿瘤血管内衬的内皮细胞中选择性表达治疗基因。最近，已经鉴定并表征了几种在肿瘤相关内皮细胞中特异性表达的基因。这些发现增强了转录靶向肿瘤内皮细胞进行癌症基因治疗的前景。在本手稿中，我们综述了用于肿瘤内皮细胞转录靶向的启动子、载体和治疗基因，并讨论了这种方法在癌症基因治疗中的前景。
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