用于药物筛选和转化研究的三维癌症模型综述

Cancer Innovation Pub Date : 2023-12-22 DOI:10.1002/cai2.102
Karthikey Sharma, Sreenath Dey, Rounik Karmakar, Aravind Kumar Rengan
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引用次数: 0

摘要

三维癌症模型填补了二维癌症模型的发现空白,在癌症研究中发挥着重要作用。除癌细胞外,基质、细胞外基质的密度和组成、癌症相关免疫细胞(如癌症相关成纤维细胞癌细胞与基质的相互作用及后续相互作用)等一系列因素(如体内肿瘤血管和类肿瘤微环境)在二维培养概念中已被广泛忽视。尽管知道这些,但继续使用单层细胞培养方法已导致一系列临床试验的失败。这篇综述讨论了肿瘤微环境(TME)再现在癌症研究中的巨大重要性,并优先讨论了肿瘤微环境要素在癌症组织病理学中的各自作用。三维模型提供的肿瘤微环境满足了体内时空排列和成分的要求,有助于分析临床前和临床试验中药物敏感性的各种不同方面,本文将讨论其中的一些方面。此外,本综述还讨论了不同 TME 元素在体外共同组装的模型,并重点研究了它们作为肿瘤的协同功能和反应性。此外,本综述还广泛介绍了最近开发的一些三维模型,这些模型的主要重点仅限于药物开发及其筛选和/或这种方法在临床前和转化研究中的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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A comprehensive review of 3D cancer models for drug screening and translational research

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research. In addition to cancer cells, a range of other factors include the stroma, density and composition of extracellular matrix, cancer-associated immune cells (e.g., cancer-associated fibroblasts cancer cell-stroma interactions and subsequent interactions, and a number of other factors (e.g., tumor vasculature and tumor-like microenvironment in vivo) has been widely ignored in the 2D concept of culture. Despite this knowledge, the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials. This review discusses the immense importance of tumor microenvironment (TME) recapitulation in cancer research, prioritizing the individual roles of TME elements in cancer histopathology. The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement, components, and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials, some of which are discussed here. Furthermore, it discusses models for the co-assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors. Furthermore, this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.

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