Division of Medical Oncology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA.
Nat Rev Clin Oncol. 2012 Apr 17;9(6):338-50. doi: 10.1038/nrclinonc.2012.61.
Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
肿瘤药物研发进展一直受到缺乏可靠的临床前模型的阻碍，这些模型可以预测新型化合物在癌症患者中的临床活性。为了克服这些缺点，最近越来越多地使用源自患者的肿瘤异种移植（PDTX）来构建免疫缺陷的啮齿动物，如无胸腺裸鼠或 NOD/SCID 小鼠，以进行临床前建模。已经建立了许多肿瘤特异性的 PDTX 模型，重要的是，它们在小鼠中传代时在全局基因表达模式、突变状态、转移潜力、药物反应性和肿瘤结构方面具有生物学稳定性。这些特征可能比标准的细胞系异种移植模型有显著的改进。这篇综述将讨论特定的 PDTX 疾病实例，概述这些模型在癌症药物开发中的机会和局限性，并描述关于预测性生物标志物开发和未来应用的概念。
