Physical Poster + E-Poster Presentation 34th Lorne Cancer Conference 2022

TRIP13 as a candidate therapeutic target in Mucinous Ovarian Carcinoma (#229)

Rita Saoud 1 2 , Olivia Craig 1 2 , Suad Abdirahman 1 2 , The Australian Ovarian Cancer Study 1 , Robert Vary 1 3 , Jennii Luu 1 3 , Jia Truong 4 , Courtney Pilcher 4 , David Asher 4 , Kaylene Simpson 1 3 , Jessica Holien 4 , Kylie Gorringe 1 2
  1. Peter MacCallum Cancer Centre, North Coburg, VICTORIA, Australia
  2. University of Melbourne, Melbourne, VIC, Australia
  3. Victorian Centre for Functional Genomics, Melbourne, VIC, Australia
  4. Royal Melbourne Institute of Technology, Melbourne, VIC, Australia

Mucinous Ovarian Carcinoma (MOC) is a rare histotype of epithelial ovarian cancer, comprising of 3-5% of all cases. It is genetically unique compared to other subtypes, with distinct precursor lesions, morphology, epidemiology, chemosensitivity and patient outcomes; and as such should be treated as a separate disease entity. Whilst 80% of cases are diagnosed at an early stage with good survival outcomes, in metastatic and recurring cases, survival is significantly worse than any other ovarian cancer subtype. This poor outcome is primarily due to resistance to traditional chemotherapies, and no approved alternative treatment. Prior network modelling and structural bioinformatics performed using a large MOC gene expression data set identified novel therapeutic targets overexpressed in MOC compared to mucinous benign tumours. Initial in vitro screening of these targets identified four candidate genes with reduced cell viability when knocked down using siRNA in MOC cell lines. This study focuses on one gene, TRIP13, which in addition to being overexpressed in several cancers, has been implicated in disease progression, relapse, poor prognosis, and most relevant to MOC, chemoresistance. We hypothesise that by inhibiting this miotic spindle assembly checkpoint protein, we can prevent cancer cell division and furthermore sensitise cells to chemotherapy. Our ongoing work utilises immunohistochemistry and western blot analysis to confirm high TRIP13 expression in MOC patient samples and cell lines, as well as cell viability assays to compare effects of siRNA knockdown and CRISPR/Cas9 knockouts to treatment with a TRIP13 specific small molecule inhibitor. Ultimately, this study may contribute to finding a new treatment option for MOC patients and significantly improve patient outcomes.