Colorectal cancer is subject to a high rate of mutations, with late stage tumors often containing many mutations. These tumors are difficult to treat, and even with the recently implemented methods of personalized medicine at modern hospitals aiming to narrow treatments, a gap still exists. Proper modeling of these tumors may help to recommend optimal treatments for individual patients, preferably utilizing a model that maintains proper signaling in respect to the derived parent tissue. In this study, we utilized an extracellular matrix-derived hydrogel to create a 3D micro-tumor construct platform capable of both supporting cells for long time durations and for high throughput drug screening. Experiments with cell lines demonstrated long-term viability with maintenance of cell proliferation. Furthermore, studies with several chemotherapeutics utilizing different mechanisms of action displayed differences in efficacy in comparing 3D and 2D cultures. Finally, patient colorectal tumor tissue was acquired and employed to reconstruct micro-tumor constructs, providing a system for the testing of novel chemotherapeutics against tumors in a patient-specific manner. Collectively, the results describe a system capable of high throughput testing while maintaining important characteristics of the parent tissue.

中文翻译：

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从细胞系和患者肿瘤生物标本中开发大肠癌3D微肿瘤构建平台，以进行护理标准和实验药物筛选。

大肠癌的突变率很高，晚期肿瘤常常含有许多突变。这些肿瘤很难治疗，即使采用现代医院针对狭窄治疗方法的个性化治疗方法，仍然存在差距。对这些肿瘤进行正确的建模可能有助于建议针对各个患者的最佳治疗方法，最好利用相对于衍生的母体组织保持适当信号传导的模型。在这项研究中，我们利用细胞外基质衍生的水凝胶来创建3D微肿瘤构建平台，该平台既可以长时间支持细胞又可以进行高通量药物筛选。用细胞系进行的实验证明了在维持细胞增殖方面的长期生存能力。此外，几种使用不同作用机制的化学疗法的研究显示，在比较3D和2D培养物时，功效存在差异。最后，获得了患者结肠直肠肿瘤组织，并将其用于重建微肿瘤构建体，从而提供了一种以患者特异性方式测试针对肿瘤的新型化学疗法的系统。总体而言，结果描述了一种能够进行高通量测试并同时保持亲本组织重要特征的系统。