Webster K R
Department of Oncology Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA.
Expert Opin Investig Drugs. 1998 Jun;7(6):865-87. doi: 10.1517/13543784.7.6.865.
With the advent of modern molecular genetics, molecular biology and biochemistry has come a revolution in oncology drug discovery research. We are rapidly developing an increased understanding in the mechanisms driving cellular proliferation, transformation, differentiation and metastasis. The hope is that from these advances will emerge novel therapeutics that are more specific, more efficacious and less toxic than their predecessors. Uncontrolled proliferation is a hallmark of a cancer cell. Over the past two decades it has become increasingly clear that molecules that directly control cell cycle progression accumulate defects during tumourigenesis. These defects can result in the loss of checkpoint control and/or the inappropriate activation of the 'drivers' of cell cycle progression, the cyclin-dependent kinases (cdks). This review will describe the recent advances in our understanding of cell cycle regulation and its relation to tumourigenesis, and highlight the potential for the development of novel anticancer therapeutics.
随着现代分子遗传学、分子生物学和生物化学的出现，肿瘤学药物发现研究迎来了一场革命。我们正在迅速加深对驱动细胞增殖、转化、分化和转移机制的理解。人们希望，基于这些进展将出现比其前身更具特异性、更有效且毒性更小的新型疗法。不受控制的增殖是癌细胞的一个标志。在过去二十年中，越来越清楚的是，直接控制细胞周期进程的分子在肿瘤发生过程中会积累缺陷。这些缺陷可能导致检查点控制丧失和/或细胞周期进程“驱动因子”——细胞周期蛋白依赖性激酶（cdks）的不适当激活。本综述将描述我们对细胞周期调控及其与肿瘤发生关系理解的最新进展，并强调新型抗癌疗法开发的潜力。
