小鼠模型在药物致癌性评价中的应用及研发人源化模型的意义

药物临床前安全性评价中的致癌实验对药物是否能进入临床实验和上市起着至关重要的作用。一些发达国家已经采用小鼠模型的短中期致癌实验作为附加实验,代替了传统的两年期实验。本文主要参考这些模型在致癌实验和药品致癌性评价中的已有数据及资料,对其特点和近年来的应用情况进行了概述。结合现有模型的缺陷,我国新药研发的需求和药物流通日益国际化的现状,得出研发DNA修复系统和细胞周期控制系统缺陷的人源化的转基因模型,是非常有前景的新替代模型。

Application of mouse models for drug carcinogenicity testing and the need for development of humanized models

Carcinogenicity tests in preclinical drug safety studies have important impact on clinical trials and mar- keting authorization for medicines. In some developed countries, short/medium term models have been used as an additional component of the potential carcinogenicity assessment, replacing the 2-year mouse bioassay. Based on the data and informa- tion obtained from chemical carcinogenicity evaluation, in this article we overview the characteristics and recent application of these models. Then faced with the shortages of these models, the demand for developing new pharmaceuticals at home and the international circulation of pharmaceuticals, we suppose that the development of new humanized models with defects in functions of DNA damage repair; Cell ~cyclc check-point appears to be very promising alternative models.