三维体外细胞培养是癌症研究中二维模型和动物模型的可行且前景广阔的替代方案。

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.96469
Andrea Esposito, Alessandra Ferraresi, Letizia Vallino, Beatrice Garavaglia, Danny N Dhanasekaran, Ciro Isidoro
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引用次数: 0

摘要

癌症是全球死亡率最高的疾病之一。癌症造成的负担不断加重,不仅影响了患者与健康相关的生活质量,还造成了巨大的全球经济影响。癌症的复杂性和异质性给研究和临床实践带来了巨大挑战,导致抗肿瘤药物临床试验的失败率上升。这部分是由于临床前模型在忠实再现人类肿瘤以作为药物疗效的可靠指标方面仍存在重大局限性。迄今为止,研发策略采用的昂贵动物模型(包括所谓的 "人源化小鼠")不仅会引发伦理问题,而且由于不能忠实再现人体生理以及患者的肿瘤微环境,往往无法准确预测对抗癌药物的反应。另一方面,传统的二维(2D)细胞培养无法充分再现肿瘤的结构组织和体内的细胞异质性。开发更精确癌症模型的必要性日益凸显,三维(3D)体外细胞培养(如癌源球形细胞和有机体)作为弥合 2D 模型和动物模型之间差距的有前途的替代方法,其重要性日益凸显。在这篇综述中,我们将简要概述三维体外细胞培养物作为临床前模型,能够在微调的微环境中正确再现体内肿瘤的组织结构、生物成分和复杂性。尽管这些模型有其局限性,但它们共同增进了我们对癌症发病机制的了解,并有可能在临床试验前对药物疗效进行更可靠的评估,从而改善癌症患者的治疗效果。
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Three-Dimensional In Vitro Cell Cultures as a Feasible and Promising Alternative to Two-Dimensional and Animal Models in Cancer Research.

Cancer represents one of the diseases with the highest mortality rate worldwide. The burden of cancer continues to increase, not only affecting the health-related quality of life of patients but also causing an elevated global financial impact. The complexity and heterogeneity of cancer pose significant challenges in research and clinical practice, contributing to increase the failure rate of clinical trials for antitumoral drugs. This is partially due to the fact that preclinical models still present important limitations in faithfully recapitulating human tumors to serve as reliable indicators of drug effectiveness. Up to now, research and development strategies employ expensive animal models (including the so-called "humanized mice") that not only raise ethical concerns, but also frequently fail to accurately predict responses to anticancer drugs because they do not faithfully replicate human physiology as well as the patient's tumor microenvironment. On the other side, traditional two-dimensional (2D) cell cultures fail to adequately reproduce the structural organization of tumor and the cellular heterogeneity found in vivo. The growing necessity to develop more accurate cancer models has increasingly emphasized the importance of three-dimensional (3D) in vitro cell cultures, such as cancer-derived spheroids and organoids, as promising alternatives to bridge the gap between 2D and animal models. In this review, we provide a brief overview focusing on 3D in vitro cell cultures as preclinical models capable of properly reproducing the tissue organization, biological composition, and complexity of in vivo tumors in a fine-tuned microenvironment. Despite their limitations, these models collectively enhance our understanding of the mechanisms underlying cancer and may offer the potential for a more reliable assessment of drug efficacy before clinical testing and, consequently, improve therapeutic outcomes for cancer patients.

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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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