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胰腺癌患者来源的异种移植模型:概述及与其他类型模型的比较

Patient-Derived Xenograft Models of Pancreatic Cancer: Overview and Comparison with Other Types of Models.

作者信息

Garcia Patrick L, Miller Aubrey L, Yoon Karina J

机构信息

Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

出版信息

Cancers (Basel). 2020 May 22;12(5):1327. doi: 10.3390/cancers12051327.

Abstract

Pancreatic cancer (PC) is anticipated to be second only to lung cancer as the leading cause of cancer-related deaths in the United States by 2030. Surgery remains the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), the most common form of PC. Multiple recent preclinical studies focus on identifying effective treatments for PDAC, but the models available for these studies often fail to reproduce the heterogeneity of this tumor type. Data generated with such models are of unknown clinical relevance. Patient-derived xenograft (PDX) models offer several advantages over human cell line-based in vitro and in vivo models and models of non-human origin. PDX models retain genetic characteristics of the human tumor specimens from which they were derived, have intact stromal components, and are more predictive of patient response than traditional models. This review briefly describes the advantages and disadvantages of 2D cultures, organoids and genetically engineered mouse (GEM) models of PDAC, and focuses on the applications, characteristics, advantages, limitations, and the future potential of PDX models for improving the management of PDAC.

摘要

预计到2030年,胰腺癌(PC)将成为美国仅次于肺癌的第二大致癌相关死亡原因。手术仍然是胰腺导管腺癌(PDAC)患者唯一可能治愈的治疗方法,PDAC是PC最常见的形式。最近的多项临床前研究致力于确定PDAC的有效治疗方法,但这些研究可用的模型往往无法重现这种肿瘤类型的异质性。用此类模型生成的数据的临床相关性尚不清楚。与基于人类细胞系的体外和体内模型以及非人类来源的模型相比,患者来源的异种移植(PDX)模型具有若干优势。PDX模型保留了其来源的人类肿瘤标本的遗传特征,具有完整的基质成分,并且比传统模型更能预测患者的反应。本综述简要描述了PDAC的二维培养、类器官和基因工程小鼠(GEM)模型的优缺点,并重点介绍了PDX模型在改善PDAC管理方面的应用、特点、优势、局限性以及未来潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b24b/7281668/ff705e4a28c3/cancers-12-01327-g001.jpg

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