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用于转移性疾病药物发现的临床前模型。

Preclinical models for drug discovery for metastatic disease.

机构信息

Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC 20007, USA.

出版信息

Cell. 2023 Apr 13;186(8):1792-1813. doi: 10.1016/j.cell.2023.02.026.

Abstract

Despite many advances, metastatic disease remains essentially uncurable. Thus, there is an urgent need to better understand mechanisms that promote metastasis, drive tumor evolution, and underlie innate and acquired drug resistance. Sophisticated preclinical models that recapitulate the complex tumor ecosystem are key to this process. We begin with syngeneic and patient-derived mouse models that are the backbone of most preclinical studies. Second, we present some unique advantages of fish and fly models. Third, we consider the strengths of 3D culture models for resolving remaining knowledge gaps. Finally, we provide vignettes on multiplexed technologies to advance our understanding of metastatic disease.

摘要

尽管取得了许多进展,但转移性疾病基本上仍是无法治愈的。因此,迫切需要更好地了解促进转移、驱动肿瘤进化以及构成先天和获得性耐药性的机制。能够重现复杂肿瘤生态系统的精密临床前模型是这一过程的关键。我们首先从同种异体和患者来源的小鼠模型开始,这些模型是大多数临床前研究的基础。其次,我们介绍了鱼类和果蝇模型的一些独特优势。第三,我们考虑了 3D 培养模型在解决剩余知识空白方面的优势。最后,我们提供了一些关于多重技术的实例,以加深我们对转移性疾病的理解。

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