Berkson Rachel G, Hollick Jonathan J, Westwood Nicholas J, Woods Julie A, Lane David P, Lain Sonia
Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
Int J Cancer. 2005 Jul 10;115(5):701-10. doi: 10.1002/ijc.20968.
Activation of the p53 tumour suppressor is predicted to have therapeutically beneficial effects. Many current anti-cancer therapies activate the p53 response via DNA damage. Non-genotoxic activation of the p53 pathway would open the way to long-term and possibly prophylactic treatments. We have established a simple protocol to screen small compound libraries for activators of p53-dependent transcription, and to select and characterise the most interesting hits, which include non-genotoxic activators. These compounds or their derivatives are of potential clinical interest. This approach may also lead to the identification of novel p53-activating compound families and possibly to the description of novel molecular pathways regulating p53 activity.
预计p53肿瘤抑制因子的激活具有治疗益处。当前许多抗癌疗法通过DNA损伤激活p53反应。p53通路的非基因毒性激活将为长期乃至预防性治疗开辟道路。我们已经建立了一个简单的方案，用于筛选小分子化合物文库以寻找p53依赖性转录的激活剂，并选择和表征最具吸引力的活性物质，其中包括非基因毒性激活剂。这些化合物或其衍生物具有潜在的临床意义。这种方法还可能导致鉴定新的p53激活化合物家族，并有可能描述调节p53活性的新分子途径。
