Curt G A
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Stem Cells. 1994 Jan;12(1):23-9. doi: 10.1002/stem.5530120107.
The process of searching for new cancer drugs has evolved from rational empiricism using high volume murine screens towards more targeted systems designed to discover agents which are specifically active against the common solid tumors of adulthood. Irrespective of the method of discovery, animal models are necessary in cancer drug development to answer fundamental questions of drug pharmacology and end organ toxicity. This knowledge is fundamental to the design of Phase I clinical trials. Increasingly, animal models are being utilized in the earliest stages of cancer drug discovery, as well as finding new uses guiding dose escalation in man. In addition, transgenic and SCID model systems have special applicability to the preclinical and clinical development of biological agents. This article reviews the emerging roles of animal models in cancer drug discovery and development.
寻找新型抗癌药物的过程已从使用大量小鼠筛选的理性经验主义,发展到旨在发现对成年常见实体瘤具有特异性活性的药物的更具针对性的系统。无论发现方法如何,癌症药物开发中都需要动物模型来回答药物药理学和终末器官毒性的基本问题。这些知识对于一期临床试验的设计至关重要。越来越多的动物模型被用于癌症药物发现的最早阶段,以及指导人体剂量递增的新用途。此外,转基因和严重联合免疫缺陷(SCID)模型系统在生物制剂的临床前和临床开发中具有特殊适用性。本文综述了动物模型在癌症药物发现和开发中的新兴作用。