Ma Guangyu, Shimada Hideaki, Hiroshima Kenzo, Tada Yuji, Suzuki Nobuo, Tagawa Masatoshi
Division of Pathology, Chiba Cancer Center Research Institute, 666-1 Nitona, Chuo-ku, Chiba, Japan.
Drug Des Devel Ther. 2009 Feb 6;2:115-22. doi: 10.2147/dddt.s3535.
Loss of p53 function compromises genetic homeostasis, which induces deregulated DNA replication, damages DNA, and subsequently results in increased resistance to anticancer agents. Pharmacological approaches using recombinant adenoviruses (Ad) have been developed to restore the p53 functions. Another approach for gene medicine is to modify Ad replication in a tumor-specific manner, which induces tumor cell death without damaging normal tissues in the vicinity. The Ad-derived gene medicines, Ad expressing the wild-type p53 gene and replication-competent Ad defective of the E1B-55kDa gene, have been tested for their clinical feasibility and became commercially available in China. These agents demonstrated their antitumor activities as a monotherapy and in combination with conventional chemotherapeutic agents. In this article, we summarize the outcomes of clinical trials in China, most of which have been published in domestic Chinese journals, and discuss potential directions of cancer gene therapy with these agents.
p53功能的丧失会损害基因稳态，进而导致DNA复制失控、损伤DNA，并随后导致对抗癌药物的耐药性增加。已开发出使用重组腺病毒（Ad）的药理学方法来恢复p53功能。基因医学的另一种方法是以肿瘤特异性方式修饰腺病毒复制，从而在不损害附近正常组织的情况下诱导肿瘤细胞死亡。表达野生型p53基因的腺病毒衍生基因药物以及E1B-55kDa基因缺陷的具有复制能力的腺病毒，已在中国进行了临床可行性测试并上市。这些药物作为单一疗法以及与传统化疗药物联合使用时均显示出抗肿瘤活性。在本文中，我们总结了中国的临床试验结果（其中大部分已发表于国内中文期刊），并讨论了使用这些药物进行癌症基因治疗的潜在方向。
