Takimoto Chris H
Department of Medicine/Oncology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7884, San Antonio, TX 78229, USA.
Cancer Chemother Pharmacol. 2003 Jul;52 Suppl 1:S29-33. doi: 10.1007/s00280-003-0623-y. Epub 2003 Jun 18.
Anticancer drug discovery and development is a rapidly evolving field. Recent advances in molecular oncology and the effort to completely sequence the human genome has led to an explosion in our understanding of the mechanisms involved in the transformation and growth of malignant cells. This in turn has led to major changes in our approach to traditional drug discovery and development. A dynamic example of how genomics is affecting cancer developmental therapeutics is provided by the ongoing changes being implemented in the anticancer drug development program run by the US National Cancer Institute (NCI). This review summarizes the history of drug screening and development efforts at the NCI over the past five decades from its inception up to its current state emphasizing molecularly targeted therapies. These changes have not only had an impact on drug discovery, but they are also providing new paradigms for the design and conduct of preclinical and early clinical trials.
抗癌药物的发现与开发是一个快速发展的领域。分子肿瘤学的最新进展以及对人类基因组进行完全测序的努力，使我们对恶性细胞转化和生长所涉及的机制的理解有了爆炸式的增长。这进而导致了我们传统药物发现与开发方法的重大变革。美国国立癌症研究所（NCI）开展的抗癌药物开发项目中正在实施的持续变革，便是基因组学如何影响癌症开发治疗学的一个生动例子。本综述总结了NCI在过去五十年从创立到当前状态的药物筛选和开发工作的历史，重点是分子靶向治疗。这些变化不仅对药物发现产生了影响，还为临床前和早期临床试验的设计与开展提供了新的范例。
