Obesity levels and liver cancer growth under the microscope

 Date: Wednesday 7th May 2014  

Cancer Council funds key research into obesity and liver cancer

New research into why overweight Australians are more likely to get liver cancer and what treatments could help stem tumour growth is being investigated as obesity and liver cancer figures continue to increase. 

Being obese or overweight is known to increase the risk of liver cancer. New research is specifically investigating why a reduced level of the hormone, adiponectin, may be linked to tumour changes in the liver.

This ground-breaking research is one of 16 research projects to be awarded a prestigious grant from Cancer Council NSW, the largest non-government cancer research funder in NSW. This year, Cancer Council NSW has committed more than $5.4m in new funding to these cancer research teams.

The additional 15 cancer research projects include research to improve outcomes for brain cancer patients, make radiotherapy more effective, identify the causes of DNA changes during cancer, and create a new blood test for cancer.

“We are funding some of the best cancer researchers in Australia, many of whom are globally renowned for their work,” said Dr Libby Topp, Research Strategy Manager, Cancer Council NSW.

“The results of these projects could help prevent cancers by identifying cancerous gene faults early and lead to more effective treatments for cancers including brain cancer, liver cancer and breast cancer.”

The research projects will run for the next three years and will involve research teams from across Australia and internationally.

“Research led by Dr Lionel Hebbard will specifically look into the role of hormones and sugars in the development and progression of liver cancer and his results will be key to identifying new and better ways to prevent and treat liver cancer,” said Dr Topp.

Recent data shows that liver cancer rates have risen by 152%1 in the past two decades, and over a similar time period, obesity rates have increased by 41%2

Dr Lionel Hebbard from the University of Sydney said: “It’s important to investigate the role obesity is playing in liver cancer as we continue to see obesity rates rising in Australia.

“Our team is delighted to be awarded this grant from Cancer Council NSW that will help us investigate why the hormone adiponectin makes liver cancer grow significantly larger, and will help us develop novel ways to treat it.”

For more information on Cancer Council NSW research visit staging.cancercouncil.com.au 

-Ends-

 Media Contact: Gina Murphy 02 9334 1428 / 0413 889 283

 *Interviews available with Dr Libby Topp, Research Strategy Manager, Cancer Council NSW and Dr Lionel Hebbard from the University of Sydney

 References

1. Australian Institute of Health and Welfare (AIHW) 2014. Australian Cancer Incidence and Mortality (ACIM) books: Liver cancer. Canberra: AIHW. <http://www.aihw.gov.au/acim-books>.                                                                                                                                                                          

2. Australian Bureau of Statistics, “4125.0 – Gender Indicators, Australia, Jan 2013”, http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/4125.0main+features3330Jan%202013

Notes to editors:

Please find a brief description of all successful grant recipients below.

How to stop Liver Cancer resisting current cancer therapies

Chief Investigator: Professor Christopher Liddle, The University of Sydney

 Liver cancer ranks 6th in incidence and 3rd in mortality worldwide. Australia has witnessed an alarming increase in the prevalence of liver cancer, and this trend will continue over the next few decades. The rising prevalence of liver cancer is largely attributed to the epidemics of viral hepatitis and fatty liver disease. The prognosis of liver cancer is poor as it is resistant to current therapies. In this project the researchers will use novel approaches to overcome treatment resistance.

Developing new therapies for breast cancer

Chief Investigator: Professor Jacqui Matthews, The University of Sydney   

 Australian women have a one-in-eight chance of being diagnosed with breast cancer during their lifetime.  Although survival rates have improved dramatically over the last few decades, thousands of Australian women still die each year from the disease. The oncoprotein LMO4 is a marker of poor prognosis in breast cancer. This work aims to develop inhibitors of LMO4 that will be used to establish the effectiveness of this protein as a drug target, and in the development of new therapeutics for this disease.

Developing a novel blood test for cancer

Chief Investigator: Dr Jeremy Hanson, Children’s Medical Research Institute

 This study further develops a novel test for cancer activity, the C-Circle test, which could assist in the management of cancer patients and improve their outcomes. The researchers will further develop the C-Circle test and make it suitable for pathology laboratories, where it could be used to detect and monitor some cancers from patient blood samples. This study will also demonstrate that the blood test improves cancer management and patient survival in paediatric bone, brain and leukaemia cancers.

Discovering the biology behind uterine cancer

Chief Investigator: Professor John Rasko, Centenary Institute

 Endometrial carcinoma is a type of uterine cancer affecting about 2000 Australian women each year. The researchers have discovered that changes in the DNA binding molecule CTCF occur in 40% of endometrial carcinoma. We already know that CTCF is required for normal gene regulation. This novel discovery indicates that CTCF plays an important role in EC development. The researchers will use various experimental approaches to determine how changes in CTCF contribute to EC development. This may provide new targets for anti-cancer therapies.

Investigating the link between obesity and liver cancer

Chief Investigator: Dr Lionel Hebbard, The University of Sydney

 Overweight individuals have an increased risk for developing a fatty liver and liver cancer. This may be due to their reduced production of the hormone adiponectin. Low adiponectin promotes changes in the metabolism of tumours. Using mice not expressing adiponectin we will test the role of important metabolic pathways in liver cancer growth. The proposed research will provide a better understanding of the factors that promote liver cancer formation and suggest novel ways to treat it.

Helping current drugs target hard to reach cancers

Chief Investigator: Dr Paul Timpson, Garvan Institute of Medical Research

Inefficient drug delivery within tumour tissue is a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D model systems of cancer, the researchers have mapped areas of poor drug delivery to distinct tumour regions. Here, the researchers will pinpoint and pharmacologically target key components of the tumour that limit efficient drug delivery. By improving drug targeting, this research aims to maximise the efficacy of anti-cancer therapeutics, in turn benefiting cancer patients and prolonging survival.

While drugs can be very effective against lone cancer cells, the complex and chaotic environment of a tumour means that drugs may not reach all the cells inside. This can mean that some cancer cells escape from the treatment, leading to the cancer coming back.

New techniques to observe cancer in bone marrow

Chief Investigator: Professor Peter Croucher, Garvan Institute of Medical Research

 Multiple myeloma is an incurable cancer of blood cells that grow in bone marrow. In the early stages myeloma cells move to bone and stay dormant until activated to grow. The researchers have developed a new technique to see single myeloma cells in living bone for the first time. They will use this to study myeloma in the early stages to see whether normal bone cells switch on these dormant cells and cause the cancer to grow. The researchers can then use bone drugs to stop myeloma from growing in patients with this disease. There are approximately 1000 new cases of myeloma diagnosed in Australia each year with 95% of patients developing painful bone lesions. Despite new myeloma-targeted therapies median survival remains poor (<4 years) and as a result new therapies are urgently required.

How one gene plays a key role in leukaemia

Chief Investigator: Professor John Rasko, Centenary Institute

 Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer and is the leading cause of cancer-related death in children. We have identified that a subset of ALL patients acquire mutations in an essential protein called CTCF. CTCF is responsible for coordinating all gene expression in the cell nucleus. The researchers will functionally test CTCF mutations, examine whether mutant CTCF promotes leukaemia development and screen for genes that drive ALL. This may reveal new targets for potential therapy.

Improving effectiveness of radiotherapy treatments for cancer patients

Chief Investigator: Professor David Thwaites, The University of Sydney 

 Advanced radiotherapy treatments use complex delivery technology to deliver high radiation doses to tumours, while minimising the dose to healthy tissues, hence improving cancer patient outcomes. These advantages are potentially limited by inherent delivery uncertainties. The researchers intend to explore the clinical impact of uncertainties, to improve the robustness of treatment methods against them, and also to assess the ability of measurement systems to detect them and hence reduce their effect.

A new use for old drugs: How do bone destruction drugs prevent cancer growth?

Chief Investigator: Professor Michael Rogers, Garvan Institute of Medical Research

Breast cancer often spreads to the skeleton and causes bone breakdown, a devastating complication for patients. Bisphosphonates are the leading class of drug used to treat this cancer-associated bone disease. In laboratory and clinical studies, these drugs can have beneficial effects beyond just blocking bone destruction and can prevent cancer growth and spread, as well as prolong survival in cancer patients. This project aims to identify exactly how these drugs have such additional benefits.

Creating treatments to reduce brain tumour size by up to 75%

Chief Investigator: Dr Megan Chircop, Garvan Institute of Medical Research

Cytokinesis is the final stage of cell division that produces two daughter cells. Incorrect localisation and modification of proteins that regulate this process cause cell division errors potentially leading to cancer. This project will investigate if dynamin II inhibitors are valid agents for treatment of brain cancers. This research will identify key dynamin inhibitory compounds with anti-cancer properties, ultimately to be used as a chemotherapy agent.

The most common type of brain tumour is Glioblastoma Multiforme (GBM), which is also the most lethal and difficult form to treat. Currently, the treatments available for GBM are very poor – they only improve survival slightly, if they work at all. New drugs and new strategies are needed to fight this cancer.

Preventing and treating skin cancer by targeting the immune system

Chief Investigator: Dr Scott Byrne, The University of Sydney 

Sunlight is the prime cause of skin cancer. Despite widespread community awareness of the need to protect ourselves from exposure to sunlight, skin cancer incidence continues to rise. We have discovered that sunlight activates a unique cell that is responsible for suppressing our cancer fighting immune system. The researchers will show using animal tumour models as well as human skin cancer patients that targeting these cells is therapeutically beneficial.

 Investigating surgery for melanomas- how much is enough? 

Chief Investigator: Professor Michael Henderson, The University of Sydney 

 The incidence of melanoma is rising. A wide excision margin is used to reduce local recurrence however more evidence is needed to know what is safe for patients with primary cutaneous melanoma >1mm in thickness. This trial will compare 1cm and 2cm wide excision margins to see if it is safe and feasible to reduce the width of excision margins, which may influence patients’ quality of life and reduce costs without impacting on recurrence or overall survival.

Research into preventing cancer cell growth

Chief Investigator: Dr Hilda Pickett, Children’s Medical Research Institute

Telomeres are protective structures at the ends of chromosomes. Activation of a telomere maintenance mechanism is a requirement of all cancer cells. We will investigate structural changes that influence how telomeres are packaged, and how these changes enable telomere length maintenance. Ultimately, the researchers aim to identify specific structural alterations that can be manipulated to prevent cancer cell growth.

Every time normal cells multiply, their chromosome ends (called telomeres) shorten slightly. Imagine a fuse – every time the cells divide, the fuse gets shorter and shorter until eventually it’s so short that the cells stop growing. This means that cells can only divide a certain number of times. Cancer cells, by definition, never stop growing (indeed, there are cancer cells from the 1950’s that are still happily growing in labs). Cancer cells overcome the limit to the number of times they can divide by finding ways to prevent telomere shortening – effectively lengthening their own fuse.

What they’re actually doing:

This research group is working on understanding how ALT works. They are doing this by using a number of chemical compounds as probes to help understand what is happening when the cells lengthen their own fuse. This is the vital first step in creating drugs that target ALT. These drugs could then be used against the 15% of cancers that use ALT to survive. As some of the tumour types that depend on ALT are currently very difficult to treat, and the outcome for patients who have these cancers is very poor, this will one day make a huge difference to a large numbers of cancer patients and their families.

A novel approach to treatment for asbestos-related cancers

Chief Investigator: Dr Glen Reid, Asbestos Diseases Research Institute

Malignant mesothelioma is a cancer with poor prognosis related to asbestos exposure. Mesothelioma patients have poor survival rates, and there is no effective treatment. This project builds on the observation that an entire family of gene regulators – so-called microRNAs – is lost in mesothelioma. Replacing them inhibits mesothelioma cell growth and increases sensitivity to chemotherapy. The aim of this project is to develop a microRNA-based drug as a new treatment option for mesothelioma.

Studying the relationship between genetics and cancer cell behaviour

Chief Investigator: Professor John Mattick AO FFA, Garvan Institute of Medical Research

 Cancer is a complex disease characterized by aberrant gene expression and genome instability. Once classified as “junk” DNA, it is now established that most of our genome encodes a class of molecules called noncoding RNAs. Noncoding RNAs, which are perturbed in cancer, coordinate the expression of other genes by controlling their accessibility in the cell. This project will discover how these RNAs function by studying their structure-function relationship in higher-order genome organisation.

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