An Advanced 3D Model of Vascularized Epithelial Ovarian Cancer in a Tumor-on-a-Chip System Based on Multi-Cell...

Epithelial ovarian cancer (EOC) is a highly lethal malignancy characterized by significant heterogeneity and poor prognosis due to late-stage diagnosis and chemotherapy resistance. Traditional two-dimensional (2D) models fail to replicate the complexity of the tumor microenvironment (TME), necessitating the development of advanced in vitro systems. Here, we present a novel microfluidic tumor-on-a-chip (ToC) system that accurately models key features of EOC, including heterogeneity and vascularization. The developed cellular model was evaluated for functionality. It was demonstrated that endothelial cells of blood vessels within a collagen matrix successfully migrated toward the cancerous tissue, while the multicellular and multilayered tumor construct secreted pro-angiogenic factors. Additionally, long-term culture conditions induced inflammatory responses, mimicking in vivo tumor progression. This innovative platform enables precise investigations into EOC biology, angiogenesis, and TME interactions. Furthermore, it holds significant potential for drug screening, assessing therapeutic efficacy, and advancing personalized oncology approaches.