药物致癌性的机制研究

Mechanism studies for carcinogenicity of pharmaceuticals

动物致癌性试验是药物非临床安全性评价的重要内容之一,在我国起步相对较晚。随着我国新药创制及相关领域的不断发展,初步具备了进行致癌性评价的条件。机制研究是致癌性评价的重要内容,结合暴露量分析、适应症与患者人群特征、同类化合物致癌性特征等进行利弊权衡,综合评估对人体的潜在风险,并最终通过说明书等方式进行风险控制。目前国际上正在着力于致癌机制的探索,有些已经被药品评价机构接受。文中对一些常见的机制研究进行总结分析,包括遗传毒性机制、药理学作用相关机制、苯巴比妥样CYP450诱导作用、致癌组织的种属差异等,以期为我国药物致癌性评价提供一定参考。

The objectives of carcinogenicity studies are to assess the tumor risk for human use.Mechanism studies are useful to evaluate the relevance of tumor findings in animal for human safety,which integrate assessment of exposure level in animal and human,nature of proposed indication and patient population,and carcinogenicity characteristic of structure-related compounds.Industries and regulatory authorities are trying to identify the mode of action（MOA） for carcinogenicity.The present review discusses several MOA,such as genotoxic mechanism,pharmacologic action related mechanism,phenobarbital-like P450 induction,and species difference in involved tissues.