Topic #355 - SBIR Phase II - A 3D Perfusable Platform for HTS Across Diverse Racial/Ethnic Cancer Spe

在美国，非裔美国人男性的前列腺癌发病率和死亡率是其他种族/民族男性的两倍。阐明这种癌症健康差异(CHD)的潜在机制对于患者治疗和改善患者预后至关重要，然而，目前还没有可用的体外模型来充分概括不同种族/民族的PCa肿瘤微环境。在第一阶段，我们的目标是通过优化3D体外模型系统的培养条件来满足这一需求。我们建立了四个PDX衍生的不同种族/民族背景的PCA模型，在持续灌流下，间质成纤维细胞和内皮血管模拟。存活至少7天后，培养物保持了表型的PCA特征，并对化疗有反应。这项研究将建立50个PCA PDX模型(非裔美国人、高加索人、西班牙人、亚洲人)，并优化肿瘤平板以及基质细胞、内皮细胞和免疫细胞的3D培养条件。将评估PCA的行为，包括细胞增殖和对化疗的反应。一旦执行，这些研究将建立PCA Oncoplate作为一个高通量筛查平台，供制药公司和学术实验室用于研究CHD，并最终为患有PCa的非裔美国人男性选择适当的治疗方法。

Prostate cancer (PCa) incidence and mortality in African American men is two times greater than men of other races/ethnicities in the United States. Elucidating the underlying mechanisms for this cancer health disparity (CHD) is critical to patient treatment and improved patient outcome, however there are no in vitro models available to adequately recapitulate the PCa tumor microenvironment across races/ethnicities. In Phase I we aimed to address this need by optimizing culture conditions of a 3D in vitro model system, the PCa OncoPlate. We developed four PDX-derived PCa models of varied racial/ethnic backgrounds with stromal fibroblasts and endothelial blood vessel mimics under continuous perfusion. Viable for at least 7 days, cultures maintained phenotypic PCa features and responded to chemotherapies. This study will establish 50 PCa PDX models (African American, Caucasian, Hispanic, Asian) and optimize 3D culture conditions in the OncoPlate along with stromal, endothelial, and immune cells. PCa behavior including cell proliferation and response to chemotherapies will be evaluated. Once executed these studies will establish the PCa OncoPlate as a high throughput screening platform for use by pharmaceutical companies and academic laboratories to investigate the CHD and ultimately select the appropriate therapeutics for African American men suffering from PCa.