Construction of Multicellular Tumor-On-A-Chip Models for Ovarian Cancer Research

Ovarian cancer remains a highly lethal gynecologic malignancy. Early diagnosis poses significant challenges, and the five-year survival rate is consistently below 45%. Current standard-of-care combines surgical resection with platinum-based chemotherapy. Emerging therapeutic modalities like chimeric antigen receptor-T (CAR-T) therapy show promise, though they face efficacy constraints due to tumor heterogeneity and immunosuppressive microenvironments. Conventional models including two-dimensional (2D) cultures and patient-derived xenografts are increasingly supplanted by organoid and tumor-on-a-chip technologies due to intrinsic limitations and poor clinical translatability. This study established multiple tumor-on-a-chip platforms derived from ovarian cancer organoids and conducted systematic in vitro drug sensitivity screening. Furthermore, by utilizing patient-derived organoids to engineer multicellular dynamic microenvironments, we achieved one of the extremely limited evaluations of CAR-T efficacy against solid tumors within ovarian cancer microfluidic systems. This work establishes an enhanced preclinical platform to advance therapeutic screening and personalized treatment development.