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不是基因疗法,而是基因手术——攻克癌症的正确策略。

Not gene therapy, but genetic surgery-the right strategy to attack cancer.

作者信息

Sverdlov E D

机构信息

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAN, Moscow, Russia.

出版信息

Mol Gen Microbiol Virol. 2009;24(3):93-113. doi: 10.3103/S089141680903001X. Epub 2009 Oct 8.

Abstract

In this review, I will suggest to divide all the approaches united now under common term "gene therapy" into two broad strategies of which the first one uses the methodology of targeted therapy with all its characteristics, but with genes in the role of agents targeted at a certain molecular component(s) presumably crucial for cancer maintenance. In contrast, the techniques of the other strategy are aimed at the destruction of tumors as a whole using the features shared by all cancers, for example relatively fast mitotic cell division or active angiogenesis. While the first strategy is "true" gene therapy, the second one is more like genetic surgery when a surgeon just cuts off a tumor with his scalpel and has no interest in knowing delicate mechanisms of cancer emergence and progression. I will try to substantiate the idea that the last strategy is the only right one, and its simplicity is paradoxically adequate to the super-complexity of tumors that originates from general complexity of cell regulation, strongly disturbed in tumor cells, and especially from the . An analysis of the most widely used for such a "surgery" suicide gene/prodrug combinations will be presented in some more details.

摘要

在本综述中,我建议将目前统一归类于“基因治疗”这一通用术语下的所有方法分为两种广泛的策略。第一种策略采用靶向治疗的方法及其所有特性,但将基因作为针对某些可能对癌症维持至关重要的分子成分的靶向剂。相比之下,另一种策略的技术旨在利用所有癌症共有的特征,例如相对快速的有丝分裂细胞分裂或活跃的血管生成,来整体破坏肿瘤。虽然第一种策略是“真正的”基因治疗,但第二种策略更像是基因手术,就像外科医生用手术刀切除肿瘤一样,对外科医生来说,他们对了解癌症发生和发展的微妙机制毫无兴趣。我将试图证实最后一种策略是唯一正确的策略这一观点,并且其简单性与肿瘤的超级复杂性形成了矛盾的契合,这种超级复杂性源于细胞调节的普遍复杂性,在肿瘤细胞中受到严重干扰,尤其是源于……将对最广泛用于这种“手术”的自杀基因/前药组合进行更详细的分析。

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本文引用的文献

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Tumor dormancy and oncogene addiction.肿瘤休眠与癌基因成瘾
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