Defining the roles of hormones in the pathogenesis of ovarian cancer
Associate Professor Pradeep Tanwar is investigating if a hormonal pill, similar to the contraceptive pill, might be developed to prevent ovarian cancer. His work has established a link between hormones and ovarian cancer – women who haven’t had children or breastfed are at increased risk of developing ovarian cancer while oral contraceptive use lowers the risk of ovarian cancer by 50 per cent. The protective effects of oral contraceptive use and pregnancy against ovarian cancer are due to high levels of progesterone hormone, which inhibits oestrogen. Pradeep’s project will define the role of ovarian hormones in the initiation, progression and spread of ovarian cancer, and determine the effectiveness of drugs that mimic the anti-cancer activity of formulations contained in oral contraceptives. The aim is to develop an ovarian cancer prevention pill but differentiate it from birth control.
THERAPEUTIC TARGETING OF THE LEADER CELL POPULATION IN OVARIAN CANCER
Hudson Institution of Medical Research
Dr Maree Bilandzic has identified a small population of the deadliest ovarian cancer cells, called ‘leader cells’. These cells lead the cancer attack on healthy tissue and have developed ways to survive and even thrive in response to cancer treatment. Dr Bilandzic’s project is investigating ways to destroy these ovarian cancer leader cells. This includes screening thousands of FDA-approved drugs not currently used to treat ovarian cancer to determine those that specifically target leader cells. This approach will ensure a rapid translation from research laboratory to treating specialists.
Targeting G9a methylatransferase to block metastasis and overcoming chemotheraphy resistance
QIMR Berghofer Medical Research Institute
Associate Professor Jason Lee is investigating new therapies to overcome treatment-resistant ovarian cancer. Recurrent, chemotherapy-resistant high-grade serous ovarian cancer (HGSOC) accounts for most deaths. Standard treatment for this type of cancer has not advanced and very little improvement in overall survival has been made. Jason hopes to change this, by developing a new drug which can cause cell death in chemotherapy-resistant ovarian cancers, and also sensitise tumours to chemotherapy. His project will also develop technology to enable earlier detection of ovarian cancer recurrence using less-invasive monitoring. This involves identifying molecular markers associated with treatment-resistant cancer that can be detected using a liquid biopsy. The aim is to also develop a method to identify patients for the right treatment – using the inhibitor, standard therapy or a combination approach.
Autoantibody Biomarkers for Ovarian Cancer Detection
Royal Adelaide Hospital and University of Adelaide
Professor Martin Oehler is Director of Gynaecological Oncology at the Royal Adelaide Hospital and a Clinical Professor of Obstetrics and Gynaecology at the University of Adelaide. His research focusses on the development of an early detection test for ovarian cancer based on patients’ immune responses. Professor Oehler has identified several autoantibodies—antibodies produced in response to the body’s own cancerous tissue—and developed a blood test to detect these. His research will now look to validate these results in a large group of patients. Professor Oehler is both a clinician and a researcher whose patients include women with ovarian cancer, which motivates him even more to find a way to improve women’s likelihood of surviving this terrible disease.
Tumour-Specific DNA Methylation in Blood for the Early Diagnosis of Ovarian Cancer
School of Women’s and Children’s Health, University of New South Wales
Dr Kristina Warton is investigating a blood test for ovarian cancer based on circulating tumour DNA. Like other cancerous tumours, ovarian cancer tumours shed DNA which spills over into the bloodstream. The DNA is different to healthy DNA because it has mutations; however, it is difficult to detect because it is so fragmented. In addition, every patient has different mutations, making it challenging to identify a common thread behind the disease. Methylation is a change that happens in cancer that seems to be quite consistent. Dr Warton is now using a cutting-edge scientific technique to amplify this circulating tumour DNA to detect methylation, and developing this in a way so it is a sensitive enough test to be detected in blood. Her research will compare blood samples of women with and without ovarian cancer.
Discovery of New Blood Protein Biomarkers for Early Detection of Ovarian Cancer
QIMR Berghofer Medical Research Institute
Associate Professor Michelle Hill is investigating an early detection test for ovarian cancer by searching for proteins in the blood which could be identified as ‘biomarkers’ of disease, and therefore translated into a clinical test. Her approach involves identifying proteins in the blood with sugars attached, called glycoproteins. Changes in these proteins have been implicated in cancer, including ovarian. Associate Professor Hill used a similar method in lab research to detect oesophageal cancer, with promising results. She is optimistic her ovarian cancer investigations will lead to findings that can be used as the basis for a blood test to detect the disease.
Multiplex Active Ratio Test for the Detection of Early Stage Ovarian Cancer
Hudson Institute of Medical Research
Dr Andrew Stephens is investigating an early detection test for one of the most serious forms of ovarian cancer. Based on a protein produced very early on in the cancer’s progression, the ‘Active Ratio Test’ (ART) is being developed as a cervical swab and potentially also a blood-based test. This research has progressed to the stage where it will be tested in a clinical trial of approximately 300 women who will be recruited from early July 2018. The ART measures the ratio between different forms of the same protein to indicate whether there is a cancer-specific modification occurring or not. The key piece of information needed from the new study is to determine how early the tumours can be detected.
Novel Strategies to Improve Outcomes of Patients with Ovarian Cancer via Nanomedicine
UQ Centre for Clinical Research, University of Queensland
Dr Carlos Solomon from the University of Queensland is focussed on developing a blood test to detect ovarian cancer early. He is investigating the role of exosomes—tiny vesicles released from cells that are believed to act as messengers to other cells—as an early indicator of the disease. Dr Solomon leads a team that has discovered exciting data over the past five years showing the possibility that exosomes are involved in cell-to-cell communication in ovarian cancer, including mediating the transformation and progression of the disease. Dr Solomon’s team has identified a set of molecules within exosomes that increase in association with the disease’s progression. Based on these molecules, an algorithm has been created to identify women at early stages of ovarian cancer using a simple blood test. This algorithm can correctly classify eight out of 10 women that will develop ovarian cancer. As a result of the OCRF funding, the University of Queensland has pledged to support a PhD student for Dr Solomon’s team to further his research.
A Novel Approach to Harness the Immune System to Battle Ovarian Cancer
School of Biomedical Sciences, University of Queensland
Dr Sherry Wu is a young researcher investigating a novel treatment for ovarian cancer. Touched by ovarian cancer patients she worked with at the University of Texas M.D. Anderson Cancer Center, who suffered from the disease’s early recurrence, her approach is investigating the ability of the body’s own immune system to recognise and attack cancer cells. By comparing ovarian cancer tumour cells containing high levels of t-cells—the immune system’s defence army—with those with low levels, Dr Wu identified it could be non-coding RNAs (molecules that don’t code for any proteins) playing a role in regulating t-cell activity. Dr Wu is now investigating whether combining this novel therapy of non-coding RNAs with existing immune therapies boosts the ability of t-cells to infiltrate and attack cancer tumour cells.
Exploring New Therapeutic Options for Epithelial Ovarian Cancers and Ovarian Granulosa Cell Tumours
Hudson Institute of Medical Research
Dr Simon Chu has been associated with the OCRF since the early 2000s and is in the third year of a three-year project, investigating an uncommon type of ovarian cancer dependent on hormones, called granulosa cell tumours. These tumours produce hormones and often the first indication a woman has this type of cancer is when abnormally high levels of oestrogen are detected. The cancer is often successfully treated, but can recur between five to 20 years later, when it becomes resistant to chemotherapy treatment. Dr Chu is investigating better treatments for these types of ovarian cancers which may also be applicable to some of the more common ovarian cancers. His approach looks at the over-expression of a particular protein in ovarian cancer (XIAP) which appears to protect a tumour cell from dying. He is investigating using combination therapy which inhibits the problematic protein XIAP before sensitising it to a further hit from another drug to cause the cancer cell death. Dr Chu has found himself serendipitously combining his expertise as an endocrinologist with research into ovarian cancer, a disease which claimed the life of his mother-in-law.