人源性肿瘤组织原位异种移植模型的特征及研究策略

Characteristics and research strategies of patient-derived orthotopic xenograft models

人源性肿瘤组织原位异种移植模型(PDOX模型)能够更好地保持原发肿瘤的基因特征,在组织学、转录组、多态性和拷贝数变异中具有高的保真度,保留了原发瘤的微血管、基质成分和相互作用,以及肿瘤转移的特点,从而更加准确地预测临床患者的疾病预后,可以筛选出最合适的个体化治疗方案,在临床转化应用研究中显示出良好的前景。但由于小鼠和人体微环境仍有差别,原位移植瘤的形态结构与原发瘤仍存在一定差别,且原位移植并不能确保肿瘤发生转移。因此,构建个体化PDOX模型就需要分析移植瘤的组织形态和相关基因的表达,建立异种移植模型的数据库,共享异种移植模型的信息与研究结果,促进PDOX模型的转化应用。本文总结了PDOX模型的主要特征,概述了其优势以及局限性,并对应用进行了展望。

The patient-derived orthotopic xenograft（ PDOX） model better maintains the genetic characteristics of the primary tumor,and keep stable in histology,transcriptome,polymorphism and copy number variations. It also retains the interaction between the tumor mesenchyma,microvessels and stroma,and the tumor metastatic properties. Therefore,PDOX model can predict disease prognosis more accurately and can be used to screen appropriate individualized treatment strategies,thus,shows perfect prospect in clinical application. However,due to the differences between mouse and human microenvironment,morphological distinctions between orthotopic xenograft tumors and primary tumors still exist,and tumor metastasis can not be ensured by orthotopic xenograft. Thus,in order to construct the individualized PDOX model and to promote its clinical translation,it is necessary to analyze the histomorphology of orthotopic xenografts,to establish database of the transplantation model and share the information of the model. In this review,we will summarize the main features of PDOX models with its advantages and limitations,and looking forward to its application in the future.