Martin D S, Balis M E, Fisher B, Frei E, Freireich E J, Heppner G H, Holland J F, Houghton J A, Houghton P J, Johnson R K
Cancer Res. 1986 Apr;46(4 Pt 2):2189-92.
Two major factors have contributed to a widely held disenchantment with murine tumor models for drug screening in cancer research: (a) the higher costs of these models in comparison to studies performed with tumor cells in vitro; and (b) the perception that these models have failed to demonstrate satisfactory correlation of chemosensitivity with analogous human tumor types; i.e., murine tumors generally have proved to be sensitive to many more agents than are found to be active in the clinic. The perceived failure of the murine models is discussed with particular reference to the difference in criteria used for evaluating drug sensitivity in murine tumor models versus clinical trials, and we conclude that the perception about murine models is not tenable in light of present information. The very important role of murine tumor models in optimizing dosage and administration schedules and, most importantly, in the development of a new drug to its most useful potential in combination chemotherapy is discussed. The value of this in vivo methodology is stressed.
在癌症研究中,有两个主要因素导致人们对用于药物筛选的小鼠肿瘤模型普遍感到失望:(a)与体外肿瘤细胞研究相比,这些模型成本更高;(b)人们认为这些模型未能证明化疗敏感性与类似人类肿瘤类型之间具有令人满意的相关性;也就是说,事实证明,小鼠肿瘤对许多药物的敏感性通常高于临床上发现有活性的药物。本文特别参照了评估小鼠肿瘤模型与临床试验中药物敏感性所采用标准的差异,讨论了小鼠模型被认为存在的不足。我们得出结论,根据目前的信息,对小鼠模型的这种看法是站不住脚的。本文还讨论了小鼠肿瘤模型在优化剂量和给药方案方面,以及最重要的是在联合化疗中将新药开发至其最有用潜力方面所发挥的非常重要的作用。本文强调了这种体内方法的价值。