Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.
Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA, USA.
Nat Rev Cancer. 2020 May;20(5):263-273. doi: 10.1038/s41568-020-0252-3. Epub 2020 Apr 6.
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.
在精准肿瘤学中，人们主要采用两种策略来预测具有临床意义的肿瘤行为，例如治疗反应和耐药性的出现：一种策略是基于对患者样本的基因组、转录组、表观基因组和/或蛋白质组分析进行推断，另一种策略是在个体化癌症模型中进行表型检测。后一种方法在历史上依赖于体内小鼠异种移植和体外类器官或 2D 细胞培养。最近在快速组合遗传建模方面取得的进展、开发用于将人类患者样本异种移植到成年斑马鱼中的遗传免疫缺陷品系，以及首次使用斑马鱼幼虫进行异种移植进行药物反应表型检测的临床试验，使这种小型脊椎动物成为精准医学领域的前沿。在这篇综述中，我们讨论了基于转基因和移植的斑马鱼癌症模型的进展，以及这些模型如何与小鼠异种移植和人类类器官相比较和互补。我们还概述了这些不同模型在预测研究中带来的独特机会，以及它们在未来临床应用中面临的挑战。
