A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids
A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids
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DOI：
10.1038/s42003-019-0305-x
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发表时间：
2019-02-25
影响因子：
5.9
通讯作者：
Soragni, Alice
中科院分区：
文献类型：
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作者：
Phan, Nhan;Hong, Jenny J.;Soragni, Alice
肿瘤类器官维持细胞间的相互作用、异质性、微环境和它们来源样本的药物反应。因此，人们对开发肿瘤类器官模型用于药物开发和个性化医疗应用的兴趣越来越大。虽然类器官原则上适用于高通量筛选，但由于技术限制和当前方法所需的大量操作，进展受到阻碍。在这里，我们介绍了一种小型化的方法，通过在井的边缘（迷你环）周围播种细胞来简化几何结构。这使得高通量筛选的格式与自动化兼容，如图所示，使用四个患者来源的肿瘤类器官，这些肿瘤类器官来自两个卵巢和一个腹膜高级别浆液性癌和一个卵巢癌肉瘤。使用我们的自动筛选平台，我们通过测量暴露于240激酶抑制剂后的类器官的活力、数量和大小来确定个性化的反应。手术后一周内可获得结果，这是一个与治疗决策相一致的时间表。
Tumor organoids maintain cell-cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Thus, there is increasing interest in developing tumor organoid models for drug development and personalized medicine applications. Although organoids are in principle amenable to high-throughput screenings, progress has been hampered by technical constraints and extensive manipulations required by current methods. Here we introduce a miniaturized method that uses a simplified geometry by seeding cells around the rim of the wells (mini-rings). This allows high-throughput screenings in a format compatible with automation as shown using four patient-derived tumor organoids established from two ovarian and one peritoneal high-grade serous carcinomas and one carcinosarcoma of the ovary. Using our automated screening platform, we identified personalized responses by measuring viability, number, and size of organoids after exposure to 240 kinase inhibitors. Results are available within a week from surgery, a timeline compatible with therapeutic decision-making.