A novel ex vivo platform for functional evaluation of treatment responses in metastatic ovarian cancer.

The lack of functional precision models that recapitulate the structural and microenvironmental features of advanced ovarian cancer remains a major barrier to improving therapeutic selection. Here, we present an organotypic mesentery membrane culture (OMMC) model, an ex vivo platform that supports rapid engraftment of freshly resected human ovarian cancer tissue and established cell lines onto intact rat mesenteric membranes. This system enables functional assessment of responses to standard-of-care therapies within five days. We demonstrate sustained viability of mesenteric tissue, successful engraftment and expansion of tumor cells and patient-derived tumor tissue, and measurable tumor-mesentery interactions. Using a multi-parametric drug sensitivity score (DSS), we quantified tumor response relative to off-target mesenteric toxicity across a panel of FDA-approved therapies. Application of the platform to patient-derived tumor samples revealed inter-patient variability in drug sensitivity profiles. Comparison of OMMC-derived responses with matched clinical outcomes suggests that this approach may help inform treatment response in a subset of cases. Together, these findings support the potential of the OMMC platform as a functional assay to complement existing preclinical and molecular approaches for evaluating therapeutic responses in ovarian cancer.