3D HUMAN TUMOR CO-CULTURE SYSTEM FOR ACCURATE Prediction of Clinical Efficacy

该提案将建立患者来源的3D共培养微肿瘤，用于筛选 抗癌治疗化合物的药物开发，导致更少的临床试验失败，因为 更早、更相关的结果，并在真实的时间内测试患者来源的样本，以做出临床决策。 我们最初的策略是建立一个与人类相关的乳腺癌微环境模型， 可以使用非破坏性手段监测和评估响应。一开始，现有 生物工程3D乳腺组织模型的寿命，对激素提示的反应，以及分析 通过并入市售的3D共培养灌注系统， 允许非破坏性的原位监测。然后我们将描述疾病状态的影响 通过用永生化的， 转化的乳腺癌细胞系中使用非破坏性分析。然后，我们将取代不朽的 细胞系与患者来源的原发性乳腺上皮肿瘤细胞，并用批准的癌症药物治疗 已知具有临床活性，以便建立基准性能和概念验证 原代人3D共培养物用于药物开发和真实的治疗的预测能力 决策。

This proposal will establish patient-derived 3D co-cultured micro tumors that will be used both to screen anticancer therapeutic compounds in drug development, leading to fewer clinical trial failures because of earlier, more relevant results and to test patient-derived samples in real time for clinical decision making. Our initial strategy will be to establish a human relevant model of the breast cancer microenvironment which can be monitored and evaluated for response using non-destructive means. Initially, an existing bioengineered 3D mammary gland tissue model¿s longevity, response to hormonal cues, and analytical evaluation improved through incorporation into a commercially available 3D co-culture perfusion system that permits non-destructive in situ monitoring. We will then characterize the effects of the diseased state (cancer) within the model by replacing the primary mammary epithelial cells with an immortalized, transformed breast cancer cell line using non-destructive analysis. Then, we will replace the immortalized cell lines with patient-derived primary breast epithelial tumor cells and treat with approved cancer drugs known to have clinical activity, in order to establish a benchmarked performance and proof of concept of the predictive power of the primary human 3D Co-cultures for drug development and real time therapeutic decision making.