Makin Guy, Dive Caroline
Cancer Research UK, Molecular and Cellular Pharmacology Group, School of Biological Sciences, University of Manchester, Manchester, UK M13 9PT.
Trends Mol Med. 2003 Jun;9(6):251-5. doi: 10.1016/s1471-4914(03)00084-4.
Major advances have been made in our understanding of the regulation of the molecular machinery of apoptosis in vitro. Molecules linking proliferation and apoptosis in healthy cells are being identified and here apoptotic cell death provides the 'fail-safe' mechanism to counteract excess proliferation. More recently, pioneering work on the regulation of apoptosis, in animal models of tumour development, has shown that suppression of apoptosis in the presence of a proliferative stimulus is sufficient for tumour development. Progress has also been made towards clarifying the contribution of drug-induced apoptosis to tumour response. With increasing evidence that failure to engage apoptosis after drug treatment contributes to drug resistance in vivo comes renewed confidence that new therapeutic approaches based on drug targets in apoptotic pathways will improve the treatment of cancer patients. As ever, tumour specificity is the major issue to be resolved.
在体外，我们对细胞凋亡分子机制调控的理解取得了重大进展。连接健康细胞增殖与凋亡的分子正在被识别，在此，凋亡性细胞死亡提供了抵消过度增殖的“故障安全”机制。最近，在肿瘤发生动物模型中有关细胞凋亡调控的开创性研究表明，在增殖刺激存在的情况下抑制细胞凋亡足以导致肿瘤发生。在阐明药物诱导的细胞凋亡对肿瘤反应的作用方面也取得了进展。随着越来越多的证据表明药物治疗后未能引发细胞凋亡会导致体内耐药性，人们重新有信心认为基于凋亡途径中药物靶点的新治疗方法将改善癌症患者的治疗。一如既往，肿瘤特异性是有待解决的主要问题。
