Sharpless Norman E, Depinho Ronald A
Departments of Medicine and Genetics, The Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.
Nat Rev Drug Discov. 2006 Sep;5(9):741-54. doi: 10.1038/nrd2110. Epub 2006 Aug 18.
Deficiencies in the standard preclinical methods for evaluating potential anticancer drugs,such as xenograft mouse models, have been highlighted as a key obstacle in the translation of the major advances in basic cancer research into meaningful clinical benefits. In this article, we discuss the established uses and limitations of xenograft mouse models for cancer drug development, and then describe the opportunities and challenges in the application of novel genetically engineered mouse models that more faithfully mimic the genetic and biological evolution of human cancers. Greater use of such models in target validation, assessment of tumour response, investigation of pharmacodynamic markers of drug action, modelling resistance and understanding toxicity has the potential to markedly improve the success of cancer drug development.
评估潜在抗癌药物的标准临床前方法存在缺陷，如异种移植小鼠模型，这已被视为将基础癌症研究的重大进展转化为有意义的临床益处的关键障碍。在本文中，我们讨论了异种移植小鼠模型在癌症药物开发中的既定用途和局限性，然后描述了应用新型基因工程小鼠模型的机遇和挑战，这些模型能更忠实地模拟人类癌症的基因和生物学演变。在靶点验证、肿瘤反应评估、药物作用的药效学标志物研究、耐药建模以及理解毒性方面更多地使用此类模型，有可能显著提高癌症药物开发的成功率。
