Feature image (L–R) | Hudson Institute Ovarian Cancer researcher, Dr Maree Bilandzic and Ovarian Cancer Research Foundation (OCRF) Ambassador and fighter, Leane Flynn
Ovarian cancer
Ovarian cancer is the tenth most common cancer in Australia, and a silent killer. It is often asymptomatic and goes undetected until the advanced stages, when the cancer is widespread.
Only a handful of new treatment options have emerged in the past 30 years, and these typically become ineffective as the cancer develops resistance to chemotherapy.
Hudson Institute’s leading researchers are focused on developing an early detection test and discovering better, more effective personalised treatments that will help people survive their diagnosis long term.
The Ovarian Cancer Research Foundation (OCRF) tissue bank at Hudson Institute is a vital resource for tackling ovarian cancer. It is one of the largest Australian repositories of ovarian cancer tumour samples for use in research, housing more than 2,448 ovarian tissue samples used to advance diagnosis and treatment.
Interferon Epsilon is a tumour suppressant and inhibits ovarian cancer
In 2004, Professor Paul Hertzog’s laboratory discovered interferon epsilon in the female reproductive tract. An interferon is a type of protein called a cytokine, which regulates the immune system. The team showed that interferon epsilon can activate immune cells to provide a protective inflammatory response to ovarian cancer in preclinical models.
Prof Hertzog’s team has since expanded on these findings with research that shows huge promise for women in the late stages of ovarian cancer who have developed chemotherapy resistance.
The latest findings published in Nature showed in pre-clinical models that administering interferon epsilon will dramatically inhibit ovarian cancer growth, particularly in cases where it has metastasised into the peritoneal cavity.
Team projects
Developing a new treatment for metastatic ovarian cancer
Identifying the role of Interferon Epsilon in the development and suppression of High Grade Serous Ovarian Cancers (HGSC)
Understanding the role of interferon epsilon, not only in ovarian cancer, but other conditions including endometriosis.
Led by Dr Andrew Stephens, the Ovarian Cancer Biomarkers research group is focused on creating a future free of ovarian cancer by developing an early detection test and better treatments to achieve long-lasting cancer remission.
“The fact is that no early detection test for ovarian cancer exists – it’s a simple necessity we owe women.” Dr Maree Bilandzic, Senior Postdoctoral Researcher
Team’s projects
Development and preclinical testing of a new cancer drug
Understanding and targeting invasive tumours
Creation of early detection tests
Combination therapies to improve patient response to current treatments
Precision medicine approaches to rapidly personalise therapy
Early detection test for women with the BRCA1 and BRAC2 gene.
Approximately five per cent of ovarian cancer sufferers have a subset of the disease known as granulosa cell tumours (GCT), which can develop at any age, even in children. The condition has a high rate of late recurrence, meaning even if surgery is effective, women live for years in constant fear that their cancer might return.
Dr Simon Chu’s Hormone Cancer Therapeutics research group is striving to bring hope to children and women with granulosa cell tumours – through better diagnosis, early detection and more targeted treatment.
“Our research will have a very real impact on people with this disease. To know that we can contribute to bringing hope to these women makes my line of work very rewarding.” Dr Simon Chu, Research Group Head.
Team projects
Identifying the genetic mutations causing the disease
Personalised treatments based on GCT molecular processes
New combination therapies to directly target GCT pathways
Establishing a cost-effective, highly specific diagnostic test
Finding gaps in patient information, clinical care and health services.
Global efforts are currently underway to identify the correlation between rare BRCA mutations and cancer occurrence – but these approaches are mainly based on the more common BRCA1 or BRCA2 mutations.
MicroRNAs are regulators of gene expression that play critical roles in many diseases including cancer. Associate Professor Michael Gantier’s laboratory discovered that molecular variations exist within a patient’s microRNA which markedly improve the accuracy of a cancer prognosis.
In this project, the team is analysing the impact of BRCA1 mutations on molecular variations of microRNAs in ovarian and breast cancer tissue from The Cancer Genome Atlas, a global directory of cancer tissue. By identifying these variations, the team aims to identify biomarkers linking BRCA1 mutations to ovarian and breast cancer.
Ovarian cancers are malignant tumours, or the uncontrolled growth of abnormal cells, in one or both ovaries. Ovaries are the female reproductive organs that produce eggs and make the hormones oestrogen and progesterone. There are three different types
1. Epithelial tumours are the most common, accounting for 90 per cent of cases, and start on the surface of the ovaries. High Grade Serous Ovarian Cancers (HGSC) are the most common form of epithelial tumours.
Age is the biggest risk factor for developing the disease
The average age for diagnosis is 64
About 1000 women die from epithelial ovarian cancer in Australia each year
The five-year survival rate is around 45 per cent – but can be as low as 10 per cent in women with fast-growing tumours.
2. Sex cord stromal tumours. The majority are granulosa cell tumours (GCT) which start from the cells that surround the eggs within the ovaries. GCT account for approximately five per cent of ovarian cancers and can develop at any age, even in children.
There are two types of GCT: adult and juvenile
GCTs are most commonly treated with surgery
Even after an effective operation, GCT can recur between five to 20 years later, and at this point are often untreatable.
These tumours often cause abnormally high levels of oestrogen in the body – causing either early puberty, an increase in abdomen size or abnormal bleeding depending on the woman’s age
One particular gene mutation causes the adult type of GCT, however the exact cause of juvenile GCT is unknown.
3. Germ cell tumours.These are the rarest tumours, accounting for about two per cent of ovarian cancers. They develop from the cells that become the eggs in the ovaries.
Signs and symptoms
Many women have no symptoms in early stage, with symptoms only appearing when the cancer has spread. Initial symptoms may include discomfort in the lower abdomen, abdominal bloating, problems with eating due to stomach compression, gas pains and backache.
Diagnosis
Tests include physical examination, blood tests, ultrasound and CT scan.
Causes and risks of ovarian cancer
Factors that increase the risk of ovarian cancer include ageing; a family history of ovarian, breast, or bowel cancer; infertility; changes in the genes BRCA1 and BRCA2 in epithelial tumours, or in the FOXL2 gene for GCT.
Stages
Early
In stage 1 the cancer is confined to one or both ovaries.
In stage 2 the cancer has spread to other organs in the pelvis.
Advanced
In stage 3 the cancer has spread beyond the pelvis to the lining of the abdomen or nearby lymph nodes.
In stage 4 the cancer has spread to other organs.
About 70 per cent of cases are diagnosed in the advanced stage.
Survival
The five-year survival rate is 45.7 per cent, but can be as low as 10 per cent in women with fast-growing tumours.
Around 4,000 women are living with ovarian cancer in Australia and about 1,000 women die from it every year.
Treatment
Treatment depends on the type of ovarian cancer and the stage. Early stage cancer is more likely to be treated successfully. Treatment may include surgery, chemotherapy and radiation therapy.
BRCA1 and BRCA2 genes in ovarian cancer
BRCA1 and BRCA2 are tumour suppressor genes that are expressed in ovarian and/or breast tissue where they work to repair DNA damage and prevent tumours forming. For women who have a mutation in the BRCA gene, DNA damage cannot be repaired. As a result, they have higher lifetime risk of developing ovarian cancer (20 per cent) and breast cancer (30 – 65 per cent), often at an early age.
Critically, for one-in-five women with a BRCA mutations, genetic based tests do not predict if they will develop ovarian or breast cancer. These mutations are too rare, and it is unknown how they impact tumour development. Therefore, understanding BRCA mutations may prevent unnecessary surgery.
Research is urgently needed to understand how tumours originate, grow, and spread. This will be used to develop better ways to prevent, detect and treat ovarian and breast cancer in women with BRCA1 and BRCA2 mutations.
Hudson Institute BRCA1 and BRCA2 research focuses on
A screening test for people with BRCA1 and BRCA2 mutations.
Finding new ways to understand the impact of rare BRCA1 mutations on tumour development.
In 2004, Professor Paul Hertzog’s laboratory discovered interferon epsilon in the female reproductive tract. An interferon is a type of protein called a cytokine, which regulates the immune system. The team showed that interferon epsilon can activate immune cells to provide a protective inflammatory response to ovarian cancer in preclinical models.
