Research Projects

PARP inhibitors are a major breakthrough in the treatment of epithelial ovarian cancer (EOC); however, 50% of the EOC that do not have HR deficiency, otherwise grouped as HR competent/proficient, response less frequently to PARP inhibitors (PARPi). Therefore, this group represents unmet clinical need and novel therapeutic strategies are needed. Preliminary work done by the PI indicate that hyperthermia and therefore HIPEC may be one of the strategies to improve chemoresponse to PARPi. In this proposal, we aim to investigate the effect of heat on PARP inhibition, HR function and NOTCH signaling in the context of i) clinical trial samples (clinical trial, which already has obtained ethical approval, will be conducted separate to this proposal) ii) ex vivo mechanistic studies on cell line and primary culture models. This will establish a concept of targeted HIPEC and a personalized therapy approach. We will use established methodologies for assessment of functional HR assay by RAD 51 foci formation and PARP immunoblot/ELISA assays previously used in clinical trials to estimate PARP activity.