文章：

癌症生物学和精确癌症治疗中的斑马鱼病人化身

Zebrafish patient avatars in cancer biology and precision cancer therapy

原文发布日期：2020-04-06

DOI: 10.1038/s41568-020-0252-3

类型: Review Article

开放获取: 否

英文摘要：

In precision oncology, two major strategies are being pursued for predicting clinically relevant tumour behaviours, such as treatment response and emergence of drug resistance: inference based on genomic, transcriptomic, epigenomic and/or proteomic analysis of patient samples, and phenotypic assays in personalized cancer avatars. The latter approach has historically relied on in vivo mouse xenografts and in vitro organoids or 2D cell cultures. Recent progress in rapid combinatorial genetic modelling, the development of a genetically immunocompromised strain for xenotransplantation of human patient samples in adult zebrafish and the first clinical trial using xenotransplantation in zebrafish larvae for phenotypic testing of drug response bring this tiny vertebrate to the forefront of the precision medicine arena. In this Review, we discuss advances in transgenic and transplantation-based zebrafish cancer avatars, and how these models compare with and complement mouse xenografts and human organoids. We also outline the unique opportunities that these different models present for prediction studies and current challenges they face for future clinical deployment.

摘要翻译： 

在精准肿瘤学领域，当前主要遵循两大策略来预测临床相关的肿瘤行为（如治疗反应和耐药性产生）：一是基于患者样本的基因组学、转录组学、表观基因组学和/或蛋白质组学分析进行推断；二是在个性化癌症替身中进行表型检测。后一方法传统上依赖于小鼠体内异种移植模型、体外类器官或二维细胞培养。近年来，快速组合遗传建模技术的进展、适用于成人斑马鱼人体样本异种移植的免疫缺陷品系开发，以及首个利用斑马鱼幼体异种移植进行药物反应表型测试的临床试验，共同推动这种微小脊椎动物站上精准医学领域的核心舞台。本文综述了基于转基因与移植技术的斑马鱼癌症替身研究进展，探讨这些模型如何与小鼠异种移植及人类类器官模型相互比较和补充，同时剖析不同模型为预测研究提供的独特机遇及其在未来临床应用中面临的挑战。

原文链接：

Zebrafish patient avatars in cancer biology and precision cancer therapy