腺病毒介导的胸苷激酶基因治疗肝癌的研究进展

Progression of recombinant adenovirus mediated herpes simplex virus thymidine kinase for the treatment of liver cancer

  • 摘要: 【摘要】 肝癌是我国常见的恶性肿瘤,针对肝癌的传统治疗方法疗效欠佳、患者预后较差。近10余年来,随着分子生物学技术的发展,肝癌的基因治疗成为该领域新的研究方向和热点,其中以腺病毒为载体的单纯疱疹病毒胸苷激酶自杀基因系统(ADV-tk)对肝癌的治疗研究开展得最早也最为广泛。其原理是把单纯疱疹病毒胸苷激酶基因通过腺病毒导入细胞内,利用其产生的酶将无毒的药物前体更昔洛韦(GCV)转变成细胞毒性产物,从而杀死肝癌细胞。多项动物实验和临床研究结果表明:ADV-tk/GCV系统是治疗肝癌的有效方法。本文总结近年来ADV-tk/GCV系统在肝癌治疗中取得的研究进展,分别从载体的发展过程、基因的作用机制、导入方式、增强杀伤效力、降低肝毒性以及相关动物模型的改进等几个方面进行综述。

     

    Abstract: Liver cancer is one of the most common malignant tumors in China. The efficacy of traditional treatment for liver cancer is unsatisfactory, and the prognosis of the patients is poor. In recent 10 years, with the development of the molecular biological techniques, genetic therapy has become a new and promising approach for liver cancer. Of which, adenovirus mediated herpes simplex virus thymidine kinase (ADVtk) for the treatment of liver cancer is widely applied. The enzyme secreted by ADVtk transformed the prodrug gancyclovir (GCV) to the cytotoxic agents and thus to kill the liver cancer cells. The results of multiple animal and clinical experiments showed that ADVtk/GCV is effective for the treatment of liver cancer. In this article, the recent progress of ADVtk/GCV in the treatment of liver cancer was reviewed.

     

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