Mucinous ovarian carcinoma (MOC) is a subtype of ovarian cancer that is completely distinct from all other ovarian cancer subtypes and for which there are no specific treatments. MOC is morphologically larger in size (>10cm) at clinical diagnosis [1], presents in a younger age group [2] and has a distinct genetic profile when compared to other histological ovarian subtypes. We have previously conducted a large-scale multi-platform genomics analysis of MOC which confirmed previous studies that mutations in the notoriously “undruggable” KRAS are the dominant mutational event [3]. However, one approach to targeting “undruggable” proteins is via their protein partners
Protein-protein interactions (PPIs) are known to play integral roles in almost all aspects of cellular function and are rapidly becoming a central focus of drug discovery in many diseases [4]. To identify novel protein-protein interactions upregulated in MOC, we created a novel bioinformatics pipeline which mapped the protein-protein interactions which differentiated MOC compared to benign cell. Importantly, we added “druggability” filters, identifying 16 protein targets that are structurally tractable to therapeutic targeting by small molecules. siRNA knockdown of these candidates in MOC cell lines and fibroblasts, identified functional proteins which inhibited cell growth in MOC cells but not fibroblasts. Furthermore, we have conducted a virtual screen on one of these targets, identifying hit compounds which bind to the protein and inhibit MOC cell growth.