Home > Liver cancer
Centenary Institute - Medical Research
Centenary Institute - Medical Research

Improving care for liver cancer patients

Researchers from the Centenary Institute and the Royal Prince Alfred Hospital (RPAH) are co-investigators on three separate liver cancer focused projects that have recently received funding from the Australian Government’s Medical Research Future Fund (MRFF) and the Cancer Institute NSW.

All projects aim to improve outcomes for patients with liver cancer, the fastest growing cancer in Australia and the world.

The two MRFF funded projects are:

Microbial based biomarkers powered by artificial intelligence for early detection of liver cancer in Australia. The Australian Liver Cancer Microbiome Consortium, $4 million. Lead institution,  University of New South Wales. Chief Investigator: Associate Professor Amany Zekry.

The IC3 Trial: Identifying Cirrhosis and Liver Cancer in Primary Care, $3.2 million. Lead institution, University of Western Australia. Chief Investigator: Professor Leon Adams.

The Cancer Institute NSW funded project is:

The APRICA program: Accelerated translational research in PRImary Liver Cancer, $4 million. Lead institution, University of Sydney. Chief Investigator: Professor Jacob George.

Professor Geoff McCaughan (pictured), Head of the Liver injury and Cancer Program at the Centenary Institute and Director of the AW Morrow Gastroenterology and Liver Centre at RPAH, is affiliated with all three projects. He was pleased to see the National and NSW Governments supporting research in such a critical health area.

“Close to 3,000 people in Australia will be diagnosed with liver cancer this year with the long-term prospects for many of these patients being quite poor. The unfortunate reality is that the five year survival rate for liver cancer is less than 20%. It’s very encouraging that both Governments have responded so positively to addressing research in liver disease, an area which has been in need of increased funding for many years.”

Professor McCaughan said the two MRFF projects, although distinct, were complementary in purpose and outlook. Both would explore new methods to detect potential liver cancer in patients at risk for hepatocellular carcinoma (HCC) at an earlier stage – and ahead of existing screening processes. 

“Early detection of cirrhosis, often a prelude to liver cancer, as well as the early detection of liver cancer itself, allows for earlier curative treatments which results in improved outcomes for patients,” said Professor McCaughan.

Professor McCaughan also noted the benefits that the APRICA program of research would deliver.

“This grant will enable best clinical care across NSW including regional communities for patients with HCC. This includes maximising prevention through to new therapies and palliative care, as well as preliminary research on the liver immune response, the microbiome and disease.”

Announcements relating to these projects can be found on the Australian Government’s Department of Health website and the website of the Cancer Institute NSW.

[ENDS]

Gene discovery suggests new treatment approach for liver cancer

In a comprehensive analysis of human gene activation data, researchers from the Centenary Institute have discovered that the dipeptidyl peptidase-4 (DPP4) gene family is strongly implicated in the development of human hepatocellular carcinoma (HCC), the most common type of primary liver cancer.

Reported in the journal ‘Cancers’, the research suggests that the DPP4 gene family and the four enzymes that it contains should be further studied to support potential new therapeutic approaches to fighting tumours found in the liver.

“In this study we interrogated a number of publicly accessible human gene databases including The Cancer Genome Atlas to identify cancers associated with the DPP4 gene family,” said Dr Hui Emma Zhang, researcher in the Centenary Institute’s Liver Enzymes in Metabolism and Inflammation Program and co-senior author on the paper.

“We were focused on the four enzymes of the DPP4 gene family– DPP4, DPP8, DPP9 and fibroblast activation protein (FAP). The role of the DPP9 enzyme was of particular interest as it hadn’t been studied previously with regard to liver cancer in humans,” Dr Zhang said.

Results from the data mining and subsequent analysis undertaken by the research team were revealing.

An association between high levels of the DPP9 enzyme and uterine and lung cancer was found suggesting that further investigatory work in both areas was required.

Elevated levels of DPP9, DPP4, FAP and DPP8 enzymes were also discovered in liver tumours and critically, were associated with poor survival rates in HCC patients.

“Our analysis indicates that high levels of all enzymes of the DPP4 family occur in liver cancers, which encourages us to target these enzymes as a possible new therapeutic approach to tackling the disease,” said Dr Zhang.

“With liver cancer incidence and mortality rates in Australia rapidly increasing new treatment options are urgently required both to improve and to save people’s lives.”

Over 2,000 Australians die each year from liver cancer. The five year survival rate for liver cancer is below 20%.

[ENDS]

Publication: DPP9: Comprehensive in silico analyses of loss of function gene variants and associated gene expression signatures in human hepatocellular carcinoma.

Centenary Institute receives Cancer Council NSW grants

Cancer Council NSW has awarded funding to 14 ground-breaking cancer research projects including three to the Centenary Institute.

Successful Centenary Institute recipients and their research initiatives are:

Professor Geoff McCaughan, Head of the Centenary Institute Liver Injury and Cancer Program. Project: A new approach to target liver cancer.

“Liver cancer is one of the deadliest cancers and is the sixth leading cause of cancer death in Australia. Current therapies for advanced liver cancer are limited and generally only grant a few months of added survival time for the patient. This project will investigate the use of combination therapies for treating liver cancer – an approach which has not yet been widely investigated. We will be using two potential new drug treatments that will target the cancer cells, the surrounding blood vessels and the immune system within the tumour,” said Professor McCaughan

Professor John Rasko AO, Head of the Centenary Institute Gene and Stem Cell Therapy Program and Royal Prince Alfred Hospital. Project: Monitoring and predicting clinical response to immunotherapy against pancreatic cancer and asbestos-induced lung cancer.

“Pancreatic cancer and mesothelioma (asbestos-induced lung cancer) are among those cancers currently lacking effective treatments, resulting in poor outcomes with five-year survival rates of less than 10%. More than 3,000 and 700 new cases of pancreatic cancer and mesothelioma, respectively, are annually diagnosed in Australia. This project will use the body’s killer immune cells (T-cells) and endow them with the information as to how to recognise and attack cancer cells (an approach known as chimeric antigen receptor T-cell therapy),” said Professor Rasko.

Dr Ulf Schmitz, Head of the Centenary Institute Computational BioMedicine Laboratory within the Gene and Stem Cell Therapy Program and University of Sydney. Project: Deciphering the cross-talk between microRNAs and retained introns in cancer gene regulation.

“This project will investigate a regulatory process known as ‘intron retention’, in both breast cancer and leukaemia. The process allows unwanted ‘junk DNA’ to enter the cell and interfere with other regulatory processes. Intron retention has been found to play a critical role in cancer development, but little is known about the underlying mechanism. Computer models and experimental methods will be used to establish how this process works, potentially opening up an entirely new field of cancer research,” said Dr Schmitz.

The Centenary Institute wishes to thank Cancer Council NSW for their support of our researchers who continue to pursue life-changing and life-saving medical research.

Full details of all successful Cancer Council NSW grants are available online here.

Successful funding for Centenary researchers

Two Centenary Institute researchers have successfully received funding grants through the Perpetual 2019 IMPACT Philanthropy program.

Prof Warwick Britton, Head of the Centenary Tuberculosis Program received funding for his project ‘Visualising how the immune system controls infection and inflammation.’

By using new imaging techniques, he hopes to be able to visualise how the immune system provokes a chronic inflammatory response in infected tissues during TB and leprosy and during immunotherapy, which can cause damage to the lung.

“Both tuberculosis and leprosy are diseases caused by the person’s immediate system reacting to the causative mycobacteria, damaging the lungs and skin/nerves respectively. Understanding how the immune cells cause this damage will help us prevent the permanent damage from these diseases. The funding from Perpetual Trustees will help us to analyse the interaction between immune cells in biopsy samples from TB and leprosy patients. This will utilise newly developed techniques using multiple antibodies to label the different immune cells in biopsy samples. The studies will be done in collaboration with clinicians in Sydney, Sri Lanka and China,” explained Prof Britton.

Dr Hui Emma Zhang received funding for her project titled, ‘Targeting unique enzyme activities for a novel therapy for liver cancer.’

“This funding will greatly facilitate my research on liver cancer, which is the third leading cause of cancer-related deaths worldwide. This funding will help me set up mouse models that recapitulate human liver cancer and evaluate the potential therapeutic benefit of novel drugs that target proteases in the liver,” says Dr Zhang.

The Perpetual 2019 IMPACT Philanthropy program distributes more than $100m annually from charitable trusts and endowments.

Improved insight into tumour growth

The Centenary Institute has collaborated with fellow medical research institute, the Hudson Institute in Victoria, to develop a novel model system for accurately monitoring tumour stage and immune cells involvement.

Head of Centenary’s Liver Enzymes in Metabolism and Inflammation Program, Professor Mark Gorrell, was involved in the research project.

Ovarian cancer develops slowly and the immune system is crucial in controlling the tumour. In this particular study, the researchers modified ovarian cancer cells so they glowed in a way that can be seen in live laboratory mice models – enabling counts of tumour cells and immune cell subsets when each tumour is removed.

This system has allowed the researchers to learn new information on tumour growth, as well as discover which immune cells are in the tumour.

The researchers plan to apply the model to other cancers, including liver cancer.

Read the full study online in scientific journal Cancers.

Learn more about how Professor Gorrell’s team at Centenary is working to help develop a new liver disease test.

New knowledge about a potential pathway for cancer therapies

Centenary Institute scientists have discovered dozens of new likely targets for a particular enzyme (FAP) that is within most tumours; paving the way for the future development of safer and more effective cancer therapies, including liver, lung, skin, colorectal and pancreatic cancers.

Instead of affecting and interacting with just collagen, the researchers have used new technologies to identify 37 molecules which FAP likely modifies.

Co-lead author, Dr Hui Emma Zhang from the Centenary Institute, says this study not only reaffirms the value of FAP in cancer research, but it also provides new avenues through which scientists can target tumour growth.

“Given FAP is fairly unique to damaged cells when compared to healthy cells, the findings from our research will enhance the initial identification and imaging of tumours, as well as provide a safer and more targeted pathway through which anti-cancer therapies can be delivered,” says Dr Zhang.

See the full media release.

Read Identification of Novel Natural Substrates of Fibroblast Activation Protein-alpha by Differential Degradomics and Proteomics in Molecular and Cellular Proteomics.

Pictured: A human liver tumour (large pale cells) surrounding a peninsular of stromal cells (dense blue), with FAP molecules stained dark brown.

A new hope for those at risk of world’s third-deadliest cancer

Centenary Institute scientists have successfully created a more realistic model of primary liver cancer; placing medical researchers in a much better position to develop more effective treatments for the third-most common cause of cancer death worldwide.

“Our novel model has progressed two key areas: fast-tracking the time it takes to conduct modelling, while more closely replicating liver cancer drivers that occur in humans,” says PhD student James Henderson, lead author on the study.

“This places researchers in a much better position to develop effective therapies in future to treat liver cancer in the early stages; reducing the burden on Australia’s health-care system and improving patient outcomes.”

Read the full media release and the published paper