Comprehensive drug efficacy data for mucinous ovarian carcinoma using a novel and extensive biobank of patient-derived organoid models

Abstract

Mucinous Ovarian Carcinoma (MOC) is a rare ovarian cancer histological subtype with distinct pathology, genomics and clinical outcomes compared to other epithelial ovarian cancers. Accordingly, there is little evidence to guide clinical care, particularly in the use of systemic therapies, and the field has lacked informative and diverse pre-clinical models. We developed MOC-specific methods for generating tumour organoids with a success rate of 70% for long-term cultured lines (n=19). Organoid lines were developed from localised, advanced and recurrent tumours, including from biopsy tissue, and represent diverse genomic features not previously captured by existing cell lines. The organoid lines were highly similar to the tumours of origin for genomic and immunohistochemical markers. Screening using a panel of 11 chemotherapy agents highlighted resistance to standard-of-care agents such as carboplatin. Gastrointestinal cancer chemotherapy agents and their combination regimens lacked activity. Paclitaxel was often highly potent at low doses but failed to kill all cells. However, less frequently used drugs such as gemcitabine, topotecan and doxorubicin inhibited many of the lines more effectively than paclitaxel. Available, but non-standard of care, chemotherapy agents should be considered for clinical management of MOC. This is the largest (by [~]10 fold) cohort of fully characterised patient-derived MOC organoid lines described and the first with extensive drug screening data affording an opportunity for drug discovery and screening for personalised treatment.