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文章:

探索结直肠癌实验模型:从二维细胞系统到类器官、人源化小鼠模型、器官芯片、CRISPR工程及人工智能驱动平台的批判性评估——转化精准肿瘤学面临的挑战与机遇

Exploring Experimental Models of Colorectal Cancer: A Critical Appraisal from 2D Cell Systems to Organoids, Humanized Mouse Avatars, Organ-on-Chip, CRISPR Engineering, and AI-Driven Platforms—Challenges and Opportunities for Translational Precision Oncology

原文发布日期:26 June 2025

DOI: 10.3390/cancers17132163

类型: Article

开放获取: 是

 

英文摘要:

Background/Objectives:Colorectal cancer (CRC) remains a major global health burden, marked by complex tumor–microenvironment interactions, genetic heterogeneity, and varied treatment responses. Effective preclinical models are essential for dissecting CRC biology and guiding personalized therapeutic strategies. This review aims to critically evaluate current experimental CRC models, assessing their translational relevance, limitations, and potential for integration into precision oncology.Methods:A systematic literature search was conducted across PubMed, Scopus, and Web of Science, focusing on studies employing defined in vitro, in vivo, and emerging integrative CRC models. Studies were included based on experimental rigor and relevance to therapeutic or mechanistic investigation. Models were compared based on molecular fidelity, tumorigenic capacity, immune interactions, and predictive utility.Results:CRC models were classified into in vitro (2D cell lines, spheroids, patient-derived organoids), in vivo (murine, zebrafish, porcine, canine), and integrative platforms (tumor-on-chip systems, humanized mice, AI-augmented simulations). Traditional models offer accessibility and mechanistic insight, while advanced systems better mimic human tumor complexity, immune landscapes, and treatment response. Tumor-on-chip and AI-driven models show promise in simulating dynamic tumor behavior and predicting clinical outcomes. Cross-platform integration enhances translational validity and enables iterative model refinement.Conclusions:Strategic deployment of complementary CRC models is critical for advancing translational research. This review provides a roadmap for aligning model capabilities with specific research goals, advocating for integrated, patient-relevant systems to improve therapeutic development. Enhancing model fidelity and interoperability is key to accelerating the bench-to-bedside translation in colorectal cancer care.

 

摘要翻译: 

**背景/目的:** 结直肠癌(CRC)仍然是全球主要的健康负担,其特点是复杂的肿瘤-微环境相互作用、遗传异质性和多变的治疗反应。有效的临床前模型对于剖析CRC生物学和指导个体化治疗策略至关重要。本综述旨在批判性地评估当前实验性CRC模型,评价其转化相关性、局限性以及在整合到精准肿瘤学中的潜力。 **方法:** 在PubMed、Scopus和Web of科学数据库中进行系统性文献检索,重点关注采用明确体外、体内及新兴整合性CRC模型的研究。根据实验严谨性以及与治疗或机制研究的相关性纳入研究。模型基于分子保真度、致瘤能力、免疫相互作用和预测效用进行比较。 **结果:** CRC模型被分为体外模型(2D细胞系、球状体、患者来源类器官)、体内模型(小鼠、斑马鱼、猪、犬)以及整合平台(芯片肿瘤系统、人源化小鼠、AI增强模拟)。传统模型提供了可及性和机制见解,而先进系统能更好地模拟人类肿瘤复杂性、免疫景观和治疗反应。芯片肿瘤和AI驱动模型在模拟动态肿瘤行为和预测临床结果方面显示出前景。跨平台整合增强了转化有效性,并支持模型的迭代优化。 **结论:** 互补性CRC模型的战略性部署对于推进转化研究至关重要。本综述为将模型能力与特定研究目标相匹配提供了路线图,倡导采用整合的、与患者相关的系统以改进治疗开发。提高模型的保真度和互操作性是加速结直肠癌诊疗从实验室到临床转化的关键。

 

 

原文链接:

Exploring Experimental Models of Colorectal Cancer: A Critical Appraisal from 2D Cell Systems to Organoids, Humanized Mouse Avatars, Organ-on-Chip, CRISPR Engineering, and AI-Driven Platforms—Challenges and Opportunities for Translational Precision Oncology

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