Recently funded projects
High throughput screens to detect new targets for ovarian cancer therapies
Hudson Institute of Medical Research
Associate Professor Ron Firestein of the Hudson Institute of Medical Research considers that to develop new targeted treatments, it is crucial to understand the processes that drive cancer cells to survive and spread — so that they can be disrupted. In collaboration with Assistant Professor Ruth Perets of Rambam Medical Centre, Israel Institute of Technology, the team will focus its project on examining PAX8 (Paired-Box Gene 8), a protein in the body responsible for many of the cancerous properties of the disease. It’s hypothesised that diminishing PAX8 could reduce the ability of cancer cells to progress. However, PAX8 has proven technically difficult to target so the team will target the proteins that drive PAX8, particularly in high grade serous carcinoma cases of ovarian cancer. Assistant Professor Perets will provide the required samples to be evaluated by Associate Professor Firestein through the use of state-of-the-art genomic technology including CRISPR screening, which enables thousands of genes to be assessed simultaneously. The team aim to determine the key drivers of the PAX8 protein and whether PAX8 not only drives ovarian cancer cells but also plays a role in the cell of origin for high grade serous carcinoma ovarian cancer. If successful, this project may open the door to new potential approaches for much needed targeted therapies.
improving the response of ovarian cancer therapy
The Olivia Newton-John Cancer Research Institute
Increased expression of the protein Hematopoietic Cell Kinase (HCK) is observed in patients with high grade serous ovarian cancer and is thought to correlate with poor survival rates. Professor Matthias Ernst of the Olivia Newton-John Cancer Research Institute will investigate whether drugs that target HCK can improve the response of ovarian cancer to existing standard-of-care therapies. The team’s previous research has shown that immune cells that have more HCK protein are better at supporting tumour growth and spread. It has also been observed that drugs that inhibit HCK activity stop the growth and spread of many different tumour types, including stomach and colon cancer. The team therefore consider that current standard-of-care drugs work much better when they are used in combination with anti-HCK drugs. This project will investigate whether anti-HCK drugs can also be combined with existing therapies to boost treatment response in preclinical models of ovarian cancer. This project holds promising potential to provide a foundation for a new targeted treatment option for high grade serous carcinoma ovarian cancer.
Currently Funded Projects
Discovery and validation of a blood-based protein biomarker for early detection
A previous OCRF supported project allowed Professor Pradeep Tanwar to collect tissue samples from women with a family history of ovarian cancer. Access to these precious samples representing the earliest stage of ovarian cancer allowed his team to uncover a promising blood-based biomarker which could be used to detect ovarian cancer in its early stages. His team’s previous work has focused on testing this biomarker in samples from patients with a family history of ovarian cancer, specifically the BRCA1/2 genes. This is because these patients, who are undergoing risk-reducing surgery, may harbour very early stages of ovarian cancer. The new biomarker has been tested on 30 women to date. In this project, funded by the OCRF, his team will now seek to validate the research further to assess whether it can achieve the specificity and sensitivity required in a larger cohort of women. To determine its accuracy, they will test their new biomarker alongside CA125, which is the only available and accepted biomarker currently, in 1000 women who have invasive or borderline ovarian cancer, and in 1000 women who do not have cancer. According to the State of the Nation Audit commissioned by the OCRF in 2020, clinicians, researchers and historical data agree that the development of a reliable early detection test of ovarian cancer could potentially save 1.3 million lives globally over the next decade.
Leveraging Genomics to overcome drug resistance in ovarian cancer.
QIMR Berghofer Medical Research Institute
Associate Professor Stacey Edwards
Associate Professor Stacey Edwards is focused on finding new and more effective treatments for ovarian cancer that also manage recurrence of the disease. Funded by the OCRF, this project focuses on high-grade serous ovarian cancer, which is the most common and aggressive type of the disease. PARP inhibitors can be used to treat this type of ovarian cancer. They work by blocking the proteins that are repairing the DNA, leading to more DNA damage and cancer cell death. However, cancer cells often turn DNA repair pathways back on, which means that patients become resistant to this type of treatment, and it stops working. Associate Professor Edwards will investigate whether combining PARP inhibitors or chemotherapy with antisense oligonucleotides (an emerging area of drug development), would improve their effectiveness. If successful, this will be the first study to identify all molecules involved in drug resistance and assess the way that they function in tumours. These results will provide evidence that combined therapies could make initial treatment of patients more effective and reduce recurrence of ovarian cancer.
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.
precision medicine for ovarian cancer
Hudson Institution of Medical Research
Women diagnosed with ovarian cancer today have few options available to them other than chemotherapy and radiotherapy treatment. While chemotherapy was considered revolutionary when it was first introduced, little has changed over the past 25 years. Meanwhile, ovarian cancer has been getting better at defending itself. This is why treatment ‘success’ is often short lived. A devastating 90% of women diagnosed at an advanced stage suffer a recurrence within 18 months of being declared in remission. With this project, Dr Stephens and his team are aiming to offer women better treatment alternatives that are designed specifically for them. The team will work with doctors to test all available drugs against a patient’s cancer, measuring both cancer response and patient effect. This will help the team to chart a specific, targeted treatment plan that will predict the changing nature of the disease to stay one step ahead of drug resistance. The project will enable doctors working with women today to collaborate with researchers working for the future of medicine, collecting patient samples that will lay the foundations for the future of personalised treatment.
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.
Early detection research will save lives
“If you can find cancer early with a test, that is literally as good as a cure because if you catch the cancer early you can cure it through surgery.”
- Dr Kristina Warton, ovarian cancer researcher
Support our research About Kristina's research
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.
Australia’s #1 charity dedicated to funding ovarian cancer research
Since 2001, we have given more than $16.5 million to Australian researchers in order to make serious inroads into understanding this insidious disease, developing an early detection test and finding new treatments.
Our impactHear the latest about our research
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 has been tested in a clinical trial of approximately 500 women recruited in Australia, as well as from Rambam Healthcare Campus and Hadassah Hospital in Israel. 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.