Mouse hospital and co-clinical trial project-from bench to bedside
Mouse hospital and co-clinical trial project-from bench to bedside
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DOI：
10.1038/nrclinonc.2015.62
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发表时间：
2015-08-01
影响因子：
78.8
通讯作者：
Pandolfi, Pier Paolo
中科院分区：
文献类型：
--
作者：
Clohessy, John G.;Pandolfi, Pier Paolo
由于癌症的分子复杂性和治疗成本，研究人员已经开始寻找体内功能基因组学来为患者护理提供信息。不幸的是，在免疫缺陷小鼠中建立的肿瘤细胞系的异种移植物未能概括人类原发性肿瘤的许多关键特征。相比之下，小鼠癌症模型通常忠实地概括了基本生物学、肿瘤-微环境相互作用、药物反应和类似于人类疾病的治疗抗性。因此，我们建立了联合临床试验项目，并在此过程中发展了小鼠医院的概念，从而使体内临床前研究和早期临床研究紧密结合，从而能够使用小鼠模型在多种癌症亚型中进行体内药物测试，同时最大限度地减少研究数千名人类患者反应所需的成本和时间。这种方法可以通知临床试验中的患者入组，并且可以使先前批准的药物重新定位和/或重新利用。
Owing to the molecular complexity of cancer and the cost of therapy, researchers have begun looking to in vivo functional genomics to inform patient care. Unfortunately, xenographs of established tumour cell lines in immunodeficient mice fail to recapitulate many critical features of human primary tumours. By contrast, mouse models of cancer often faithfully recapitulate basic biology, tumour-microenvironment interactions, drug responses and therapy resistance similar to human disease. Thus, we established the co-clinical trial project, and in doing so developed the concept of the mouse hospital, whereby in vivo preclinical and early clinical studies are closely aligned, enabling in vivo testing of drugs in a multitude of cancer subtypes using mouse models, while minimizing the cost and time required to study responses in thousands of human patients. This approach can inform enrolment of patients in clinical trials, and can enable repositioning and/or repurposing of previously approved drugs.