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

话题

• 批准号: 10022040
• 负责人: Anthony Saleh
• 金额: $ 200万
• 依托单位: MIMETAS US, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2021-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022040
• 关键词: 3-Dimensional; Address; African American; Asians; Behavior; Biological Models; Blood Vessels; Caucasians; Cell Proliferation; Cells; Coculture Techniques; Collection; Complex; Drug Screening; Endothelial Cells; Endothelium; Ethnic Origin; Fibroblasts; Growth; Hispanics; Immune; Incidence; Laboratories; Malignant Neoplasms; Malignant neoplasm of prostate; Modeling; Patient-Focused Outcomes; Patients; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Race; Small Business Innovation Research Grant; Therapeutic; Time; United States; cancer health disparity; chemotherapy; high throughput screening; improved; in vitro Model; men; mortality; prostate cancer model; racial and ethnic; racial diversity; response; three dimensional cell culture; tumor microenvironment

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.

非裔美国男性的前列腺癌（PCa）发病率和死亡率是美国其他种族/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结局至关重要，但是没有体外模型可用于充分概括跨种族/种族的PCa肿瘤微环境。在第一阶段，我们旨在通过优化3D体外模型系统PCa OncoPlate的培养条件来满足这一需求。我们开发了四个PDX衍生的PCa模型的不同种族/民族背景与基质成纤维细胞和内皮血管模拟下连续灌注。培养物存活至少7天，保持表型PCa特征并对化疗有反应。本研究将建立50个PCa PDX模型（非洲裔美国人、高加索人、西班牙裔、亚洲人），并优化OncoPlate中的3D培养条件沿着基质细胞、内皮细胞和免疫细胞。将评价PCa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作为高通量筛选平台，供制药公司和学术实验室用于研究CHD，并最终为患有PCa的非洲裔美国男性选择适当的治疗方法。