Article Text
Abstract
Introduction Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian cancer (EOC) comprising <5% of cases. Despite its rarity MOC contributes significantly to the poor outcomes seen with EOC due to its inherent resistance to platinum-based chemotherapy regimens. Heated intraperitoneal chemotherapy (HIPEC), where a single dose of heated chemotherapy is given at surgery, has gained traction in recent years following benefits seen in high grade serous ovarian carcinoma and colorectal carcinoma. Data on the use of HIPEC in MOC remains limited.
Methods Following the development of successful MOC organoid models, we undertook drug screening with eight chemotherapy agents often used in HIPEC. To simulate HIPEC conditions, we incubated our organoid models at 43C for 120 minutes following addition of the chemotherapy agent. Drug response was evaluated using CellTiter-Glo and Brightfield imaging.
Results In the HIPEC model, platinum-based chemotherapy appears to have a cytostatic effect on MOC organoids in comparison to normothermic conditions. Variable responses were seen to gemcitabine, mitomycin C and 5FU with the addition of heat having no therapeutic effect. Strongest response was seen to irinotecan with the addition of heat again having no additional effect.
Conclusion/Implications Utilising organoids to assess HIPEC chemotherapy regimens in MOC provides a unique opportunity to assess drug response. HIPEC appears to improve response to platinum-based chemotherapy in MOC organoids whilst having little additional benefit with other agents. Going forward we aim to assess further combination chemotherapy regimens and to correlate results with genetic and gene expression characteristics to further understand treatment response.