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自杀基因疗法在癌症和 HIV-1 感染中的应用:传统治疗方法的替代选择。

Suicide gene therapy in cancer and HIV-1 infection: An alternative to conventional treatments.

机构信息

Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; University of Strasbourg, Research Unit 7292, DHPI, IUT Louis Pasteur, Schiltigheim, France.

University of Strasbourg, Research Unit 7292, DHPI, IUT Louis Pasteur, Schiltigheim, France.

出版信息

Biochem Pharmacol. 2022 Mar;197:114893. doi: 10.1016/j.bcp.2021.114893. Epub 2021 Dec 28.

Abstract

Suicide Gene Therapy (SGT) aims to introduce a gene encoding either a toxin or an enzyme making the targeted cell more sensitive to chemotherapy. SGT represents an alternative approach to combat pathologies where conventional treatments fail such as pancreatic cancer or the high-grade glioblastoma which are still desperately lethal. We review the possibility to use SGT to treat these cancers which have shown promising results in vitro and in preclinical trials. However, SGT has so far failed in phase III clinical trials thus further improvements are awaited. We can now take advantages of the many advances made in SGT for treating cancer to combat other pathologies such as HIV-1 infection. In the review we also discuss the feasibility to add SGT to the therapeutic arsenal used to cure HIV-1-infected patients. Indeed, preliminary results suggest that both productive and latently infected cells are targeted by the SGT. In the last section, we address the limitations of this approach and how we might improve it.

摘要

自杀基因治疗(SGT)旨在引入一种基因,该基因编码一种毒素或一种酶,使靶细胞对化疗更敏感。SGT 代表了一种对抗传统治疗方法失败的疾病的替代方法,例如胰腺癌或高级别神经胶质瘤,这些疾病仍然极具致命性。我们回顾了使用 SGT 治疗这些癌症的可能性,这些癌症在体外和临床前试验中显示出了有希望的结果。然而,SGT 在 III 期临床试验中迄今为止已经失败,因此需要进一步改进。我们现在可以利用 SGT 在治疗癌症方面的许多进展来对抗其他疾病,例如 HIV-1 感染。在综述中,我们还讨论了将 SGT 添加到用于治疗 HIV-1 感染患者的治疗武器库中的可行性。事实上,初步结果表明,SGT 可以靶向增殖性和潜伏性感染细胞。在最后一节中,我们讨论了这种方法的局限性以及如何改进它。

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