微流控芯片赋能个性化癌症诊疗的研究进展

Advances in Microfluidic Chip-Enabled Personalized Cancer Diagnosis and Therapy

摘要: 肿瘤精准治疗的发展对体外药效评估模型的生理相关性和预测可靠性提出了更高要求。传统二维细胞培养和动物模型在反映肿瘤微环境复杂性及个体差异方面存在明显局限，难以满足个体化用药决策和联合治疗策略优化的需求。近年来，患者来源模型(Patient-Derived Models, PDMs)与微流控芯片技术的融合，为构建高仿生、可控且具有转化潜力的体外肿瘤研究平台提供了新的解决思路。该类平台能够在微尺度空间内重建肿瘤微环境的关键组成要素，实现肿瘤细胞、免疫细胞及基质成分的动态互作，并支持对抗肿瘤药物疗效、治疗反应差异及耐药机制的系统评估。已有研究表明，基于患者来源微流控模型的体外评估结果与临床治疗结局具有较好的相关性，在疗效判别、联合用药筛选及个体化治疗方案优化方面显示出明确的应用潜力。本文系统综述了患者来源模型与微流控芯片的主要整合策略，重点总结其在抗肿瘤治疗反应评估、耐药机制解析及转化应用中的研究进展，并讨论当前面临的标准化、可重复性及临床转化挑战，以期为微流控肿瘤模型在精准药学研究和个体化治疗决策中的进一步应用提供参考。

Abstract: The development of precision oncology requires in vitro efficacy assessment models with high physiological relevance and reliable predictive power. Conventional 2D cell culture and animal models often fail to capture the complexity of the Tumor Microenvironment (TME) and inter-patient heterogeneity, limiting their utility for individualized treatment decisions and optimization of combination strategies. In recent years, the integration of Patient-Derived Models (PDMs) with microfluidic chip technology has provided a new solution for constructing controllable, biomimetic, and translational platforms that reconstruct key TME components at the microscale, support dynamic tumor-immune-stroma interactions, and facilitate systematic evaluation of anti-tumor drug efficacy, therapeutic response variability, and resistance mechanisms. Accumulating evidence indicates that treatment responses measured in patient-derived microfluidic models correlate well with clinical outcomes, highlighting their potential for response stratification, combination screening, and regimen optimization. This review summarizes major integration strategies between PDMs and microfluidic chips, highlights recent progress in anti-tumor therapeutic response assessment, resistance dissection, and translational applications, and discusses remaining challenges in standardization, reproducibility, and clinical implementation, thereby providing a reference for the further application of microfluidic tumor models in precision pharmacy research and individualized therapeutic decision-making.