Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Cancer Res Treat. 2018 Jan;50(1):1-10. doi: 10.4143/crt.2017.307. Epub 2017 Sep 13.
Establishing an appropriate preclinical model is crucial for translational cancer research. The most common way that has been adopted by far is grafting cancer cell lines, derived from patients. Although this xenograft model is easy to generate, but has several limitations because this cancer model could not represent the unique features of each cancer patient sufficiently. Moreover, accumulating evidences demonstrate cancer is a highly heterogeneous disease so that a tumor is comprised of cancer cells with diverse characteristics. In attempt to avoid these discrepancies between xenograft model and patients' tumor, a patient-derived xenograft (PDX) model has been actively generated and applied. The PDX model can be developed by the implantation of cancerous tissue from a patient's tumor into an immune-deficient mouse directly, thereby it preserves both cell-cell interactions and tumor microenvironment. In addition, the PDX model has shown advantages as a preclinical model in drug screening, biomarker development and co-clinical trial. In this review, we will summarize the methodology and applications of PDX in detail, and cover critical issues for the development of this model for preclinical research.
建立合适的临床前模型对于癌症转化研究至关重要。迄今为止,最常用的方法是移植源自患者的癌细胞系。尽管这种异种移植模型很容易产生,但存在几个局限性,因为这种癌症模型不能充分代表每个癌症患者的独特特征。此外,越来越多的证据表明癌症是一种高度异质性的疾病,因此肿瘤由具有不同特征的癌细胞组成。为了避免异种移植模型与患者肿瘤之间的这些差异,人们积极地生成和应用了患者来源的异种移植(PDX)模型。PDX 模型可以通过将患者肿瘤的癌变组织直接植入免疫缺陷小鼠中来开发,从而保留细胞间相互作用和肿瘤微环境。此外,PDX 模型在药物筛选、生物标志物开发和临床试验方面作为临床前模型具有优势。在这篇综述中,我们将详细总结 PDX 的方法学和应用,并涵盖为临床前研究开发该模型的关键问题。