p53-based Cancer Therapy
p53-based Cancer Therapy
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DOI：
10.1101/cshperspect.a001222
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发表时间：
2010-09-01
影响因子：
7.2
通讯作者：
Lain, Sonia
中科院分区：
文献类型：
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作者：
Lane, David P.;Cheok, Chit Fang;Lain, Sonia
p53 功能失活几乎是人类癌细胞的普遍特征。这激发了开发基于 p53 的癌症疗法的巨大努力。使用腺病毒载体传递的野生型 p53 进行基因治疗目前在中国得到广泛应用。其他生物学方法包括开发旨在仅复制和杀死 p53 缺陷细胞的溶瘤病毒，以及开发 siRNA 和反义 RNA，通过抑制负调节因子 Mdm2、MdmX 和 HPV E6 的功能来激活 p53。肿瘤细胞中发生的 p53 加工过程的改变可以引发 T 细胞和 B 细胞对 p53 的反应，从而有效消除癌细胞，基于 p53 的疫苗目前正在进行临床试验。许多直接或间接激活p53反应的小分子也已到达临床，其中最先进的是p53 mdm2相互作用抑制剂。对 p53 反应的更多了解也有助于开发强大的药物组合，通过选择性保护正常细胞和组织来提高化疗的选择性和安全性。
Inactivation of p53 functions is an almost universal feature of human cancer cells. This has spurred a tremendous effort to develop p53 based cancer therapies. Gene therapy using wild-type p53, delivered by adenovirus vectors, is now in widespread use in China. Other biologic approaches include the development of oncolytic viruses designed to replicate and kill only p53 defective cells and also the development of siRNA and antisense RNA's that activate p53 by inhibiting the function of the negative regulators Mdm2, MdmX, and HPV E6. The altered processing of p53 that occurs in tumor cells can elicit T-cell and B-cell responses to p53 that could be effective in eliminating cancer cells and p53 based vaccines are now in clinical trial. A number of small molecules that directly or indirectly activate the p53 response have also reached the clinic, of which the most advanced are the p53 mdm2 interaction inhibitors. Increased understanding of the p53 response is also allowing the development of powerful drug combinations that may increase the selectivity and safety of chemotherapy, by selective protection of normal cells and tissues.