A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture.
A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture.
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DOI：
10.1158/0008-5472.can-21-0799
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发表时间：
2022-02-01
期刊：
影响因子：
11.2
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中科院分区：
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具有6孔板设计的Cancer-on-Chip平台结合硅基微流体技术，可以通过多个肿瘤切片的平行培养和使用原发性肿瘤材料的诊断测定来实现最佳的患者特异性治疗策略。癌症的最佳治疗需要诊断方法来促进治疗选择并防止无效治疗。直接评估存活肿瘤标本的治疗反应可以填补这一诊断空白。因此，我们设计了一种微流体平台，用于在精确控制的生长条件下使用肿瘤组织切片评估患者治疗反应。优化的癌症芯片（CoC）平台维持了乳腺和前列腺肿瘤切片的活力和持续增殖7天。在此时间范围内未观察到组织形态或基因表达模式的重大变化，表明CoC系统提供了一种可靠有效的方法来探测肿瘤的内在化疗敏感性。定制的CoC平台分别准确预测了乳腺和前列腺肿瘤异种移植模型中顺铂和apalutamide的治疗反应。乳腺癌的培养期可以延长至14天，而组织形态和活力没有重大变化。这些文化特征使治疗结果的评估和详细的机制研究开放的可能性。具有6孔板设计的Cancer-on-Chip平台结合硅基微流体技术，可以通过多个肿瘤切片的平行培养和使用原发性肿瘤材料的诊断测定来实现最佳的患者特异性治疗策略。
The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material. Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.