Vascularized tumor explants for drug testing

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Project Abstract Our understanding of cancer progression or response to therapies would benefit from easily accessible, patient- specific assays that recapitulate the biology and anatomy of human tumors. To this end, we will develop methodology for integrating tumor explants with engineered stroma and vasculature in vitro. With appropriate culture conditions, a self-assembled vascular network develops and then incorporates into co-cultured tumors excised from mice or patients. The system provides a representative extracellular matrix, associated stromal cells, and a lumenized vessel network. The methodology is straightforward and amenable to high throughput assays, making it an attractive tool for in vitro drug screening or for the guidance of patient-specific chemotherapies. Using this approach, we propose to create a platform for optimally maintaining samples from patients with pancreatic ductal adenocarcinoma (PDAC) ex vivo in vascularized tumor explants (VTEs) for the purpose of biological analysis and drug testing. We will characterize the VTEs and validate the system using mouse xenograft models and surgical tissue samples from PDAC patients treated at the MGH Cancer Center. When complete, this project will establish a robust, high throughput, and validated platform for analyzing tumor biology or drug testing, thus accelerating cancer research and enabling personalize therapy for cancer.