Sausville Edward A, Burger Angelika M
Marlene and Stewart Greenebaum Cancer Center, and Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 22 S. Greene Street, Baltimore, MD 21201, USA.
Cancer Res. 2006 Apr 1;66(7):3351-4, discussion 3354. doi: 10.1158/0008-5472.CAN-05-3627.
Mouse models of cancer have consistently been used to qualify new anticancer drugs for study in human clinical trials. The most used models include transplantable murine tumors grown in syngeneic hosts and xenografts of human tumors grown in immunodeficient mice. For the latter systems, retrospective preclinical-clinical correlation studies are available, which suggest that improvements must be made to increase their value. Transgenic, knock-out, and knock-in mouse models and their intercrosses are more recent developments that mirror defined steps of human carcinogenesis. However, their value in predicting clinical results remains to date poorly defined. We take the position that properly used and interpreted human tumor xenografts grown in immunodeficient mice can be useful, although not absolutely predictive of behavior in the clinic, and continue to make contributions to critical clinical development choices.
癌症小鼠模型一直被用于鉴定新的抗癌药物，以便在人类临床试验中进行研究。最常用的模型包括在同基因宿主中生长的可移植鼠肿瘤，以及在免疫缺陷小鼠中生长的人类肿瘤异种移植。对于后一种系统，有回顾性临床前-临床相关性研究，这些研究表明必须进行改进以提高其价值。转基因、敲除和敲入小鼠模型及其杂交是较新的进展，反映了人类致癌作用的特定步骤。然而，它们在预测临床结果方面的价值至今仍定义不明确。我们的立场是，在免疫缺陷小鼠中生长的人类肿瘤异种移植，如果使用得当并得到正确解释，可能会有用，尽管不能绝对预测临床行为，但仍会继续为关键的临床开发选择做出贡献。
