Gynaecological Cancer Research

Lab head: Anna deFazio
Location: Westmead Institute for Medical Research

Our research focus is on a group of cancers that occur in women, in particular ovarian cancer. Ovarian cancer has a low overall survival rate, but treatment response varies between patients. Our research is centered on understanding the molecular drivers of ovarian cancers, understanding what determines response to treatment and on identifying signatures that predict response to treatment.

Research approach equipment: Cell culture: Including a range of new and well-established cell lines, IncuCyte live cell imaging, proliferation and apoptosis assays Tissue based research: Fixed and frozen tumour and normal tissue samples (GynBiobank), tissue microarrays Gene expression: RNAseq, NanoString, Digital droplet PCR Genomics / Mutation testing: Next-generation sequencing Proteomics / Protein expression: immunohistochemistry, Western Blots, SWATH-MS

Predictors of endocrine treatment response in low-grade serous ovarian cancer

Primary supervisor: Anna deFazio deFazio

Low-grade serous carcinoma (LGSC) is a subtype of ovarian cancer that tends to occur in younger women and does not respond to current standard chemotherapy. Recent data showed improved survival in LGSC patients on endocrine  treatment. However, it is still not clear which endocrine treatments are most the effective nor is it possible to predict which patients will respond.

A proportion of LGSC will respond to endocrine treatment and molecular signatures can be identified that will predict response.

1. To test response to endocrine therapy such as tamoxifen and fulvestrant in a panel of LGSC cell lines with differing underlying oncogenic mutations.
2. To determine the association of endocrine response with tumour expression of estrogen (ER) and progesterone receptor (PR) isoforms, and known and novel gene signatures, that we hypothesize will be predictive of response to endocrine therapy.

Using RNAseq analysis of tumours from ovarian cancer patients who have shown an objective response to hormone treatment compared those who have shown no response, we have developed a novel gene signature that we hypothesize will be predictive of response to endocrine therapy (Mapagu et al, in preparation). We will use a panel of LGSC cell lines to determine response to endocrine therapy such as tamoxifen and fulvestrant and to test and refine the response signature. The signature will be tested in retrospective LGSC cohorts to determine the proportion and characteristics of LGSC cases that would be predicted to be hormone responsive; in clinical trial samples of LGSC patients treated with hormone therapy; and prospectively in newly recruited patients. The expected outcome is a robust, validated signature to test in a prospective LGSC clinical trial of hormone treatment.

Discipline: Applied Medical Sciences, Westmead
Co-supervisors: Anna deFazio deFazio, Cristina Mapagu, Tania Moujaber
Keywords: Ovarian cancer, Gene expression, Gynaecological cancer