Melbourne researchers harness the bodys own defences to stop ovarian cancer

In a research breakthrough published in the prestigious journal Nature, Melbourne scientists have revealed the results.

Professor Paul Hertzog's research group at Hudson Institute of Medical Research has been working to expand on their discovery of a naturally occurring signalling protein found in the female reproductive tract, Interferon epsilon and its potential application in treatment of this deadly disease.

Their work involves harnessing the body's own system of signalling proteins to fight ovarian cancer.

Dr Nicole Campbell has been working for several years on understanding how these treatments which target the body's immune system can be optimised to improve its ability to fight the tumour.

"Immunotherapies have been very successful in the treatment of other types of cancer, but they have had limited success in ovarian cancer - we're looking to change that," Dr Campbell said.

"We know that in High Grade Serous Ovarian Cancers (the commonest form of ovarian cancer) tumour cells recruit and activate 'immunosuppressive' cells which prevent anti-tumour immune cells from killing tumour cells, so we're aiming to develop new therapeutics which can reverse that process and improve survival rates."

Professor Hertzog said that last year more than 1000 Australians died of ovarian cancer, and the likelihood of living more than five years with the disease is still less than 50 per cent.

"It is often diagnosed late, and the most common treatments have limited effectiveness, with resistance to chemotherapy a major factor. It is a disease where new insights were needed, Prof Hertzog said."

Dr Campbell's work in the study of Interferon epsilon also formed the PhD project of Dr Zoe Marks, which established that the protein protects against ovarian cancer via tumour cells as well as the body's immune system.

This work was co-supervised by post-doctoral scientist Dr Nollaig Bourke, from Trinity College Dublin, who found that women with high grade serous ovarian cancer no longer had the normal expression of interferon epsilon.

"This was really interesting to us as we knew that interferon epsilon was part of a family of proteins known for their anti-tumour activities and we wondered what would happen if we could try restore this lost expression," Dr Bourke said.

"We tried giving interferon epsilon back to help block the growth of ovarian cancer cells and therefore prevent the growth of primary and secondary tumours. The results were very striking, confirming that interferon epsilon was a very effective tumour suppressor in ovarian cancer," Dr Bourke said.

Prof Hertzog explained that since his laboratory's discovery of Interferon epsilon in 2004, a great deal of progress has been made with Hudson Institute leading the world.

"At Hudson Institute we are now able to produce pure IFN-, which allows us to conduct incredibly valuable research into how and where it can be used most effectively," he said.

"We now know that Interferon epsilon is naturally made in the epithelium lining organs such as the female reproductive tract where it acts as a natural booster of immunity to infections. Our recent discovery is that it also acts as a tumour suppressant, and that it is lost during the process of ovarian tumour formation.

"We know from pre-clinical models that administering it will dramatically inhibit ovarian cancer growth, particularly in cases where the cancer has metastasised into the peritoneal cavity," Prof Hertzog said.

A new blood test is being developed to improve ovarian cancer diagnosis, with the potential to reduce unnecessary surgery leading to better health outcomes, saving time, stress and money for patients and the healthcare system.

Hudson Institute of Medical Research, funded by the Ovarian Cancer Research Foundation, has developed a new diagnostic test for ovarian cancer, which is now being commercialised by ASX bound Australian company Cleo Diagnostics Ltd.

Cleo will advance the availability of its cancer diagnostics platform, which is designed to eventually address all ovarian cancer detection markets with specific tests including surgical triage, recurrence, high risk, and early-stage screening. The test will now enter a development phase and undergo validation prior to clinical use.

The blood tests will be underpinned by a patented novel biomarker, CXCL10, which is produced early and at high levels by ovarian cancers, but not in non-malignant disease. CXCL10 was first identified at Hudson Institute by Dr Andrew Stephens, who is now Cleo's Chief Scientific Officer.

Initial clinical use will focus on the surgical triage market to improve treatment outcomes for patients with ovarian cancer, and simultaneously avoid unnecessary surgery and anxiety for women with far more common non-cancerous conditions. Beyond surgical triage, Cleo Diagnostics will conduct further clinical trials to evaluate the effectiveness of the underlying core technology for disease recurrence following surgery and ultimately aims to develop broader screening applications in the general population.

There is no accurate and reliable detection test for ovarian cancer - a pap test does not detect ovarian cancer. Ovarian cancer is the most lethal of all cancers affecting women in Australia, and a silent killer. The current five year survival rate is 49% and this has not changed substantively in 50 years.

Ovarian cancers are often indistinguishable from common, non-cancerous disease. Currently patients undergo a combined CA-125 blood test and ultrasound to provide an assessment of disease.

However, neither is sufficient for an accurate diagnosis and they are only used for surgical referral. Invasive surgery to remove the ovaries remains the only way to definitively diagnose the presence of malignant disease.

As a result, a large proportion of women experience a cancer scare, undergoing unnecessary anxiety, trauma and invasive surgery due to the lack of accurate diagnostic technology.

The Cleo surgical Triage Test is being developed as an easy to administer blood test that accurately distinguishes benign from malignant disease without surgical intervention. The potential benefits are significant:

Improved early evaluation of patients using a simple blood test, that provides an actual cancer diagnostic assessment before surgery is considered;

High specificity and sensitivity to identify cancer, allowing efficient referral of patients to an appropriate gynecological oncology surgeon for treatment;

Patients that are diagnosed with non-cancerous growths will benefit from more conservative management strategies; and

Substantial reduction in stress and anxiety experienced by women who undergo a 'cancer scare' and must wait for a surgical diagnosis.

CLEO Diagnostics, Lead Medical Advisor, Professor Tom Jobling, said: "There is often a delay in sending patients to a gynaecological oncology specialist for treatment, because defining whether a growth is likely to be malignant or not before surgery is very difficult. This new test will help ensure that an optimal management plan can be put in place early, which will streamline the referral process and provide the best care for patients. This also extends to patients with benign conditions, where early identification will permit direction to more appropriate use of resources."

Pending regulatory approval, the CLEO Triage Test also has the potential to provide significant benefits to the broader community, including:

Cost savings in the health care system (government, hospital, health insurance); Improved care for women with non-cancerous tumours;

More efficient allocation of priority surgical beds; and

Community benefits associated with reduced hospital stays.

Hudson Institute's chief executive, Professor Elizabeth Hartland, said: "Hudson Institute is delighted to be partnering with Cleo Diagnostics to take our work on ovarian cancer one step closer to delivering a much-needed diagnostic test. We thank the OCRF for being a long-term and dedicated supporter of this research."

Ovarian Cancer Research Foundation chief executive Robin Penty said: "Through ongoing community support, the OCRF is proud to have nurtured this research from the lab bench through to the commercialisation phase. We are excited to see where Cleo takes it from here."

Cleo Diagnostics recently closed a successful IPO to list on the Australian Securities Exchange (ASX). This funding will provide a runway over the next two years to enable a blood test to be built, validated and made available for initial clinical triage use in 2025, with a staged execution strategy to other target markets until it is widely available.