Personalized Organoid-Chip Model For Drug Testing in Pancreatic Cancer

用于胰腺癌药物测试的个性化类器官芯片模型

基本信息

批准号：
10570699
负责人：
Faraz Bishehsari
金额：
$ 22.88万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10570699
关键词：
3-Dimensional Adjuvant Antineoplastic Agents Basic Science Biological Assay CD8-Positive T-Lymphocytes Cancer Biology Cancer Patient Cancerous Cell Communication Cell Differentiation process Cells Characteristics Clinical Clinical Trials Complex Decision Making Devices Disease Progression Drug Delivery Systems Drug Modelings Drug Targeting Elements Endothelium Environment Epithelium Failure Fibroblasts Fibrosis Genes Goals Human Immune Immunotherapy Individual Interruption Macrophage Malignant Neoplasms Malignant neoplasm of pancreas Modeling Molecular Molecular Profiling Organ Organoids Outcome Pancreatic Ductal Adenocarcinoma Pathogenicity Pathology Pathway interactions Patient-Focused Outcomes Patients Pharmaceutical Preparations Phenotype Prediction of Response to Therapy Resistance Role Series Solid Neoplasm Source Survival Rate System T-Lymphocyte Technology Testing Therapeutic Tissues Tumor Immunity Tumor Promotion Vascularization cancer immunotherapy cancer therapy cancer type cell type chemotherapy cohort conventional therapy design drug development drug efficacy drug testing experimental study functional outcomes improved in vivo individual response individualized medicine innovation malignant breast neoplasm microfluidic technology molecular modeling next generation novel novel therapeutics organ on a chip pancreatic cancer model pancreatic stellate cell patient subsets personalized medicine personalized strategies pre-clinical protein expression real time monitoring research and development response stellate cell stem cells targeted treatment therapy resistant treatment response tumor tumor behavior tumor microenvironment tumor progression

项目摘要

ABSTRACT In order to improve cancer patient outcomes, the next generation of cancer therapeutics should combine targeted treatments with the ability to predict the likelihood of an individual’s tumor to benefit from a given treatment. The focus of this project is on advancing a personalized platform based on the individual’s tumor behavior which is determined not only by the cancerous epithelium but the entire tumor microenvironment (TME). The role of TME in disease progression or even therapeutic drug response is well established in variety of cancers with poor outcome including pancreatic ductal adenocarcinoma (PDA) with a five year survival rate of less than 10%. Here, combining 3D patient-derived organoids (PDO) and microfluidic technologies, we will develop a novel tumor-chip device with the potential to generate individualized treatment response predictions ex vivo. In Aim 1, using multiple tissue and functional read outs we will show that our multicellular platform recapitulates the tumor and its microenvironment. In Aim 2, we will show the utility of our system as an individualized ex vivo platform to functionally characterize the tumor response to conventional and novel therapies. Our long-term goal is to optimize patient-specific ex vivo drug response assay technology such that it may be used to rapidly, accurately, and reliably inform individualized treatment decisions. As a proof of concept, the project involves developing a personalized pancreatic cancer model; however this technology can be extended to other solid tumor types with rich TME (i.e., breast cancer) to improve molecular and/or cellular characterizations of cancer biology and therapeutics.

抽象的为了改善癌症患者的治疗结果，下一代癌症治疗方法应结合能够预测个体肿瘤从给定治疗中受益的可能性的靶向治疗该项目的重点是开发基于个体肿瘤的个性化平台。行为不仅由癌性上皮决定，而且由整个肿瘤微环境决定 (TME) 在疾病进展甚至治疗药物反应中的作用已在多种疾病中得到充分证实。预后不良的癌症，包括具有五年生存率的胰腺导管腺癌 (PDA) 在这里，我们将结合 3D 患者源性类器官 (PDO) 和微流体技术。开发一种新型肿瘤芯片设备，有可能产生个性化的治疗反应预测在目标 1 中，我们将使用多种组织和功能读数来展示我们的多细胞平台。在目标 2 中，我们将展示我们的系统作为一个系统的实用性。个性化的离体平台，用于功能表征肿瘤对传统和新型药物的反应我们的长期目标是优化患者特异性体外药物反应测定技术，以便它可用于快速、准确、可靠地为个体化治疗决策提供信息作为证据。概念上，该项目涉及开发个性化胰腺癌模型；然而，这项技术可以扩展到具有丰富 TME 的其他实体瘤类型（即乳腺癌），以改善分子和/或细胞癌症生物学和治疗学的特征。