Introduction Mucinous ovarian carcinoma (MOC) is a rare cancer with poor outcomes when advanced due to innate resistance to standard of care platinum-taxane chemotherapy regimens. There is a lack of evidence to support different chemotherapy choices due to poor clinical trial recruitment and a scarcity of suitable pre-clinical models. Our objective was to develop new patient-derived models of MOC and use them to test therapies.
Methods We collected tissue samples with consent from women undergoing surgery for primary or recurrent MOC. We optimised culture conditions for growing tumour cells as 3D organoids in Matrigel, which included specific growth factors and processing conditions. Successful cultures were characterised by immunohistochemistry (CK7, CK20, PAS, PAX8, p53, HER2) and DNA and RNA sequencing for comparison to the original tumour. Organoids were tested with 14 therapeutic agents and evaluated using CellTiter-Glo, brightfield imaging and Hoechst staining.
Results We successfully cultured eight MOC as organoid lines that showed strong concordance with tumour genetic and protein characteristics. Drug screening showed little response to platinum-based chemotherapies. Variable responses were seen with paclitaxel, mitomycin C and gemcitabine, with the strongest responses observed with topoisomerase I inhibitors irinotecan and topotecan.
Conclusion/Implications This is the first cohort of organoid models for MOC tested across a wide range of chemotherapeutic agents. Results support clinical observations of limited response to platinum chemotherapy, while other therapies show some promise as alternatives. Future work will explore combinations of agents as well as correlation back to genetic and gene expression characteristics to assess biomarkers of response.
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