Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancers. LGSOCs are notoriously slow-growing, therefore many chemotherapies that target pro-proliferative pathways are ineffective compared to responses seen in high-grade serous ovarian carcinomas (HGSOC). Difficulties in identifying effective treatments and late diagnosis often lead to poor prognoses for LGSOC patients.
The WEHI-Stafford Fox Rare Cancer Program (SFRCP) receives biological samples from patients with a variety of rare gynaecological cancers, including LGSOC. Currently, 30 of the 656 SFRCP patients have LGSOC. Our patient-derived xenograft (PDX) project aims to generate pre-clinical models of rare gynaecological cancers. These models build sustainable banks of patient tumour tissue for molecular analyses such as whole genome sequencing (WGS). Using this data, we can advise treatments based on the tumour profiles and indicate eligibility for specific clinical trials. Tumours from PDX models are also used to generate cell-lines and organoids for drug screens. In future, we hope to use this data to provide clinical treatment guidance to improve patient outcomes. Due to the slow-growing nature of LGSOC, unfortunately we have not had success in generating PDX models from any LGSOC tumours in the Program.
Despite difficulties in producing PDX models, our lab has successfully developed one cell-line derived from a primary patient sample. We have validated this cell-line by sequencing and immunohistochemistry (IHC). This cell-line has a BRAF (V600E) mutation, which is present in 16% of LGSOC (1). Activating mutations in mitogen-activated protein (MAPK) pathway are common in LGSOC, however, responses to inhibitors, such as MEK inhibitors (MEKi), are often poor. We hope to use this cell-line to look for synergistic MEKi combinations that may be effective in the treatment of LGSOC. We also hope that by comparing the WGS data from the LGSOC cases with that of other tumour types studied in the SFRCP, we will be able to determine what genetic traits are unique to LGSOC, better directing the course of treatment for LGSOC patients. This poster shows a snapshot of the pipeline from patient sample to sequencing in the SFRCP and summarises the importance of developing appropriate models of LGSOC.