Abstract 2795: Ex vivo modelling of vascularized pdx-derived ovarian tumors

Predicting clinical response to anticancer drugs remains a major challenge in cancer therapy research. The current treatment of patients with ovarian cancer involves surgery and platinum-based chemotherapy, which still result in recurrence on advanced stages of the disease. During tumor progression, cancerous cells continuously accumulate mutations giving rise to a heterogeneous population of cells. Additionally, spatial distribution of stromal, endothelial and immune cells in the microenvironment affects tumor progression, cell morphology, and ultimately drug response. In order to predict clinical outcome of chemotherapy in vitro, tumor heterogeneity and microenvironment constituents must be conserved. Current models of tumor biology and microenvironment consist in xenografts of human tumors implanted in immunodeficient mice. These models allow studying systemic treatment response, but its application is limited to small developmental studies. Here, we present a high throughput in vitro 'grafting' platform where we co-culture blood vessels with tumor explants. Each unit in this platform is composed of two parallel microfluidic channels and a central chamber. Two endothelial tubules are generated in the microfluidic channels and cultured in presence of a gradient of angiogenic factors (S1P, VEGF, bFGF and PMA) added to the central chamber of the culture unit. Angiogenic tubules form vascular beds within 3-5 days, after which tumor explants are loaded to the central chamber on top of the vascular beds. The model shown in this study consists of ovarian serous papillary adenocarcinoma collected after xenograft growth in immunodeficient mice. This ovarian cancer explant was previously characterized as resistant to Paclitaxel. In this study, we observe how the vascular bed remodels in the presence of the explant and closely interacts with ovarian tumor tissue. Vessel perfusion and stabilization of vascular bed was monitored by real time imaging of 150 kDa FITC-Dextran. Cultures were evaluated by assessment of morphology and presence of endothelial and tumor cell biomarkers. Moreover, co-culture response to Sorafenib (anti-angiogenic), Palbociclib and Paclitaxel was detected by distinctive proliferation rates as compared to control conditions. The established ovary cancer-on-a-chip platform enables the study of fundamental aspects of tumor disease and progression. In addition, these co-cultures serve as a platform for understanding tumor-endothelial cell crossta