研究动态
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弥合肿瘤仿真器与临床之间的鸿沟:15年研究的系统综述。

Bridging the gap between tumor-on-chip and clinics: a systematic review of 15 years of studies.

发表日期:2023 Aug 18
作者: Charlotte Bouquerel, Anastasiia Dubrova, Isabella Hofer, Duc T T Phan, Moencopi Bernheim, Ségolène Ladaigue, Charles Cavaniol, Danilo Maddalo, Luc Cabel, Fatima Mechta-Grigoriou, Claire Wilhelm, Gérard Zalcman, Maria Carla Parrini, Stéphanie Descroix
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

在过去的15年里,肿瘤学研究领域在新型细胞培养模型的发展方面取得了重要进展,例如肿瘤芯片(ToC)系统。在这篇全面概述中,我们汇集了物理学家、生物学家、临床医生和制药公司的专家,从多学科角度展示ToC研究的当前状态、其独特特点以及面临的挑战。为了为读者提供对ToC领域的清晰而定量的理解,我们对2005年至2022年间与ToC相关的300多篇出版物进行了广泛的系统分析。ToC模型通过实现对各种参数的精确控制,具有其他体外模型所不具备的关键优势。这些参数包括细胞外基质的特性、对细胞施加的机械力、物理化学环境、细胞组成以及肿瘤微环境的结构。这种精细控制使得ToC能够密切模拟肿瘤内的复杂微环境和相互作用,以高度真实的方式研究癌症进展和治疗反应。重要的是,通过纳入来自患者的细胞或肿瘤异种移植物,ToC模型在临床验证方面展示了有希望的结果。我们还研究了ToC在制药行业中的潜力,预计ToC的采用将逐渐增加。展望未来,鉴于临床试验的高失败率和对3R原则(代替、减少、改进动物实验)的日益重视,ToC模型在癌症研究方面具有巨大潜力。在接下来的十年里,通过ToC模型产生的数据有可能用于发现新的治疗靶点,为监管目的做出贡献,改进临床前药物测试并减少对动物模型的依赖。
Over the past 15 years, the field of oncology research has witnessed significant progress in the development of new cell culture models, such as tumor-on-chip (ToC) systems. In this comprehensive overview, we present a multidisciplinary perspective by bringing together physicists, biologists, clinicians, and experts from pharmaceutical companies to highlight the current state of ToC research, its unique features, and the challenges it faces. To offer readers a clear and quantitative understanding of the ToC field, we conducted an extensive systematic analysis of more than 300 publications related to ToC from 2005 to 2022. ToC offer key advantages over other in vitro models by enabling precise control over various parameters. These parameters include the properties of the extracellular matrix, mechanical forces exerted on cells, the physico-chemical environment, cell composition, and the architecture of the tumor microenvironment. Such fine control allows ToC to closely replicate the complex microenvironment and interactions within tumors, facilitating the study of cancer progression and therapeutic responses in a highly representative manner. Importantly, by incorporating patient-derived cells or tumor xenografts, ToC models have demonstrated promising results in terms of clinical validation. We also examined the potential of ToC for pharmaceutical industries in which ToC adoption is expected to occur gradually. Looking ahead, given the high failure rate of clinical trials and the increasing emphasis on the 3Rs principles (replacement, reduction, refinement of animal experimentation), ToC models hold immense potential for cancer research. In the next decade, data generated from ToC models could potentially be employed for discovering new therapeutic targets, contributing to regulatory purposes, refining preclinical drug testing and reducing reliance on animal models.