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用于结直肠癌个体化医学的患者来源异种移植模型。

Patient-derived xenograft models for personalized medicine in colorectal cancer.

机构信息

General Surgery, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, Zhejiang, China.

Department of Gastroenterology, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, 310014, Zhejiang, China.

出版信息

Clin Exp Med. 2020 May;20(2):167-172. doi: 10.1007/s10238-020-00609-4. Epub 2020 Feb 25.

Abstract

Establishing superior preclinical models is critical for translational cancer research owing to the high failure rates of novel therapeutics in clinical studies. Even though cell line-derived xenograft models are easy to create, they have numerous limitations since these models do not represent the distinctive features of each cancer patient adequately. To circumvent the discrepancies between xenograft models and tumors, patient-derived xenograft (PDX) models have been developed. These models are established through the engraftment of tissue from a patient's tumor into an immune-deficient mouse, which preserves cell-cell interactions and tumor microenvironment. Since PDXs precisely replicate intratumoral heterogeneity, a range of chemotherapeutic agents can be tested on individual tumors. Colorectal cancer represents a unique case to demonstrate clinical perspectives revealed by PDX models since they surmount limitations of conventional ex vivo models. Even though PDX models have been associated with drawbacks with respect to prediction of clinical outcomes, they are currently the model of choice for preclinical investigations in colorectal cancer. In the current review, we provide an overview of the methodology and applications of PDX for colorectal cancer and discuss critical issues for the advancement of these models for preclinical research.

摘要

建立优越的临床前模型对于癌症转化研究至关重要,因为新型治疗方法在临床研究中的失败率很高。尽管细胞系衍生的异种移植模型易于创建,但由于这些模型不能充分代表每个癌症患者的独特特征,因此存在许多局限性。为了避免异种移植模型与肿瘤之间的差异,已经开发了患者来源的异种移植(PDX)模型。这些模型是通过将患者肿瘤的组织植入免疫缺陷小鼠中建立的,从而保留了细胞间相互作用和肿瘤微环境。由于 PDX 精确地复制了肿瘤内的异质性,可以在单个肿瘤上测试各种化疗药物。结直肠癌是一个独特的案例,可以展示 PDX 模型揭示的临床观点,因为它们克服了传统离体模型的局限性。尽管 PDX 模型在预测临床结果方面存在一些缺点,但它们目前是结直肠癌临床前研究的首选模型。在当前的综述中,我们提供了 PDX 用于结直肠癌的方法学和应用概述,并讨论了这些模型在临床前研究中进展的关键问题。

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