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Research for every stage of the cancer journey

2012 Research Profile

www.cancercouncil.com.au

Welcome Research for every stage of the cancer journey Thank you. Your continued support is helping to bring us closer to our goal of defeating cancer, and it is wonderful to know we share the same vision and commitment to funding world-class cancer research.

It is my pleasure to be sending you the 2012 Cancer Council Research Profile. As an independent, not-for-profit organisation that receives almost no government funding, we rely on our supporters to continue our important work. And so I hope you will enjoy reading about some of the projects we are proud to be supporting this year because it is thanks to your generosity that we are able to keep funding ground-breaking research into cancer and its causes.

The impact of a cancer diagnosis on individuals and their families is as shocking as ever, with 36,000 people diagnosed each year in NSW alone. Cancer Council is determined to reduce the number of cases, increase cancer survival rates and improve the quality of life for all cancer patients through our focus on the four aspects of cancer action: Prevention, Diagnosis, Treatment, and Survivorship.

Vision

Cancer defeated Our vision will be realised when lives are not cut short nor the quality of life diminished by cancer.

Mission

To defeat cancer through engaging the community Find out more: In this Research Profile 2012 edition you will find examples of Cancer Council’s innovative and exciting research projects.

For more information about these and other projects please visit our website at cancercouncil.com.au

Each of the projects you will read about in the 2012 Cancer Council Research Profile addresses one of these important areas and represents part of the $16 million Cancer Council NSW will spend this year supporting cutting-edge cancer research.

Your support is a key factor in enabling the success of these new projects and the continuation of existing studies. Along with the hard work and dedication of the many researchers whose work you help fund, I have no doubt we will be able to achieve significant outcomes in the near future and come closer to our vision of a future without cancer.

I would like to take this opportunity to thank you once again for your continued support and commitment. Without it, the worldclass research we will fund in the coming year would simply not be possible, and along with it the chance to make a real difference to the lives of those who have been touched by cancer.

The cancer Journey Our approach to research is unique, as we cover all types of cancer and address all aspects of cancer action, providing hope to everyone touched by cancer.

Prevention Diagnosis Treatment Survivorship

Dr Andrew G Penman, AM CEO, Cancer Council NSW 1

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Prevention

Using models for cancer screening and prevention

Risk and prognostic factors of glioma in Australia

Associate Professor Karen Canfell, Cancer Research Division, Cancer Council NSW

Associate Professor Gianluca Severi, Epidemiology Centre, Cancer Council Victoria

AIM: To find the most cost effective health programs to help defeat cancer.

AIM: To better understand what causes brain cancer.

The Cancer Modelling group, led by Associate Professor Karen Canfell, is investigating the best ways to prevent cancer, with a focus on cervical cancer. Using mathematical models to predict the long-term outcome of different prevention methods such as cancer screening and human papillomavirus (HPV) vaccinations, the group hopes to answer questions such as ‘How often should women get screened for cervical cancer?’ and ‘What is the most cost-effective way to prevent cervical cancer?’

Glioma is the most common type of primary brain tumour in adults, accounting for more than 80% of brain and central nervous system cancers. It is currently incurable and presents a significant health burden in Australia; despite this, its cause is still unknown in most cases.

The modelling group is part of a worldwide group of collaborators known as Modellers Sans Frontières. Focusing on cervical cancer, the group has already developed simulations of HPV infection which have helped policymakers make informed choices about how to vaccinate adolescents against the disease. The team’s research has also been very influential in several policy decisions regarding cervical cancer screening programs in Australia, the UK and New Zealand.

In the near future, the research team is proposing to investigate how HPV testing and Pap smears can be used in the most costeffective way to prevent cervical cancer.

“Modelling is a key factor in our ability to best use the cancer resources available in our community. The cervical cancer modelling we’ve done has already opened the door to a wide range of opportunities to improve cancer prevention here and around the world, and I truly believe we can help save many more lives.”

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Prevention

This project hopes to improve our knowledge of what causes glioma and what affects its progression. Associate Professor Gianluca Severi and his team will recruit 800 glioma patients and 800 healthy family members from across Australia to form one of the largest epidemiological studies of glioma in the world.

The researchers will collect information on the lifestyle of the participants as well as their family history of cancer. They will also ask participants to donate a blood sample which will be used to search for genes that are responsible for this cancer.

This information will help identify what increases the risk of getting glioma and whether a particular lifestyle choice or genetic mutation is responsible.

Dr Severi’s research aims to help identify people at high risk of the disease. This will open up opportunities for prevention, earlier diagnosis, and better treatments. Importantly, by storing the DNA of glioma patients, the project will create a resource that can be used by other researchers across Australia.

“Glioma is so aggressive and causes enormous grief, yet we can’t do much at the moment to help patients and their families.

That’s what drives me to do this research: the hope that we can improve cancer control, prevention, and clinical practice.”

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Diagnosis

Investigating protein behaviour to improve treatments

Mechanisms underpinning how brain cancer cells respond to drugs

Dr Sue Firth, Hormones and Cancer Division, Kolling Institute of Medical Research

Dr Kerrie McDonald, Cure For Life Neuro-oncology Group, Lowy Cancer Research Centre, University of NSW

AIM: To understand how cancer cells survive in stressful conditions.

AIM: To help predict how brain cancer will respond to treatment.

Cancer cells are often under stress because of their fast and unpredictable growth. In order to survive and thrive within the body, they have a number of ‘tricks’ they use to stay alive in stressful conditions. One of these tricks is autophagy, where a cell will ‘self-digest’ its damaged or unnecessary parts. This allows the cancer cell to survive starvation, lack of oxygen, and even the effects of chemotherapeutic drugs or radiation. As any cells that survive chemotherapy are more difficult to treat, preventing this behaviour could make treatments more effective.

Glioblastoma (a type of brain cancer) is extremely resistant to radiotherapy and chemotherapy. Almost all glioblastomas regrow in the brain after treatment, often even nastier than before. This is why the survival rate for glioblastomas is so low, with patients living on average only 15 months.

Dr Sue Firth and her research team have found a protein that breast cancer cells may use to promote autophagy and survive stressful situations. Called IGFBP-3, it is associated with aggressive breast cancers and may hold the key to understanding cancer autophagy. By investigating IGFBP3’s behaviour, Dr Firth and her team will greatly improve our understanding of how cancer cells escape treatment.

If IGFBP-3 is shown to protect cancer cells, it would be a prime target for treatments. It would also help create diagnostics to define breast cancer subtypes, enabling clinicians to identify tumours that are most likely to respond to autophagy inhibitors, improving treatments and making it much less likely that the cancer will return.

“When tumours grow beyond a certain size they face a lack of oxygen and nutrients, but they still seem to survive. Once we can understand how this survival process happens, this will give us a handle on how to stop it.”

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Diagnosis

A better understanding of how glioblastoma becomes resistant to treatment would help clinicians predict how a patient will respond to a particular therapy, leading to better drug selection and improved overall survival. Glioblastoma is a very diverse disease – two cancers that look the same can respond very differently to drugs. Worse, the brain cancer cells that survive the first treatment are often genetically different when they re-emerge.

This project will begin to unravel this diversity by looking deeply at the genetics behind it. Dr Kerrie McDonald and her team have already discovered a subtype of glioblastoma that is significantly easier to treat. Expanding on this, they hope to find genes that can help predict treatment efficiency in all glioblastoma patients.

Knowing which treatments work best on each subtype would allow clinicians to more accurately diagnose and treat brain cancer patients, substantially improving treatments. This could mean longer survival and better quality of life for patients.

“We’re on the verge of coming up with some pretty useful clinical changes. You don’t need motivation to work in brain cancer - if you can just make one small improvement it’s all worthwhile.”

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Diagnosis

Immune system behaviour and its role in cancer diagnosis

Activating a tumour suppressor for leukaemia therapy

Associate Professor Stuart Tangye, Immunology and Inflammation Program, Garvan Institute of Medical Research

Dr Nicole Verrills, University of Newcastle

AIM: To improve immune responses to cancer.

People with problems with their immune systems are 300 times more likely to develop cancer than the normal population, highlighting how key the immune system is in preventing cancer. X-linked lymphoproliferative disease (XLP) is an immune deficiency that makes people extremely susceptible to disease caused by the Epstein-Barr virus. This virus is carried by over 90% of the world population and is normally relatively harmless; however in XLP patients it often leads to cancer.

Associate Professor Stuart Tangye’s research looks at why this is the case. His team has already found molecules that could be used to treat the Epstein-Barr virus infection in XLP patients.

If they can restore the immune system so that it is able to fight the virus, they will have found the first step towards a therapy to treat lymphoma in XLP patients.

This research has wider applications, as infection with EpsteinBarr virus is associated with a number of other cancers including Burkitt’s lymphoma, nasopharyngeal carcinoma, and Hodgkin’s disease. Understanding how the immune system normally prevents the Epstein-Barr virus from causing cancer could lead to better diagnostics and treatments for these cancers.

“To me the immune system is central to everything as it protects us from infectious disease. Unfortunately a consequence of infectious disease can be problems like cancer. We’re working on what it takes to turn on the immune system to give you a really good immune response to the Epstein-Barr virus, which is known to cause lymphoma.”

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Treatment

AIM: To test innovative new treatments for acute myeloid leukaemia.

Acute myeloid leukaemia (AML) accounts for over 30% of leukaemia diagnosed in Australia yet it has one of the lowest survival rates - only 18% of males and 25% of females diagnosed will survive.

This research team, led by Dr Nicole Verrills, has developed two exciting new treatments for this difficult cancer. Current leukaemia treatments try to stop a particular gene from working, however these methods often do not work on AML. Dr Verrills’ team of researchers are trying to activate a protein called PP2A that normally suppresses cancers but is turned off in AML. By developing two drugs that can turn PP2A back on and enable it to fight the cancer, Dr Verrills hopes to find a new treatment for the disease.

The next step will be to test these drugs in pre-clinical trials.

More research will also be done into exactly how the drugs work, which will help clinicians to use them effectively. It may also lead to future drugs that are even better PP2A activators. This is important, as PP2A is silenced in a range of other leukaemia and solid tumours, so if these drugs work they could have a remarkable impact on treatment for a range of other cancers.

“What I think is unique about our research is that we’re working on a protein that is only relatively newly recognised as being important in any cancer, let alone leukaemia. We hope that this research will lead to new clinical trials and ultimately better outcomes for AML patients.”

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treatment

The role of telomerase in cancer development and treatment

Beta-catenin intracellular transport and its role in cell polarity and migration

Associate Professor Tracy Bryan, Cell Biology Unit, Children’s Medical Research Institute

Dr Beric Henderson, Gene Expression Laboratory, Westmead Institute for Cancer Research

AIM: To understand how to stop cancer cells growing indefinitely.

AIM: To study new ways of controlling a key cancer-causing protein inside the cell.

Normal cells in the body can only divide a certain number of times before they stop multiplying. Cancer cells, however, can replicate themselves almost indefinitely. This research group is looking at how cancer cells keep dividing, and how to prevent this from happening.

Dr Beric Henderson and his team are helping us understand a key cancer protein, beta-catenin, which may lead to completely new cancer treatments.

A specific part of cell DNA known as the telomere is key to this unlimited growth. When a normal cell divides, the telomere gets shorter. When it gets too short, the cell stops dividing. Research has found that 85% of cancers have a protein called telomerase that reverses this process. A treatment that could stop telomerase from working could stop the growth of cancer cells entirely.

Telomerase is an exciting target for new cancer treatments. If it can be blocked it could help treat everything from leukaemia to pancreatic cancer. And, because most normal cells have undetectable levels of telomerase, any treatments that stop it working will have fewer side effects than current chemotherapy.

Associate Professor Tracy Bryan and her team are investigating ways to regulate telomerase and possibly turn it off altogether.

Another protein, DHX36, could also be necessary for cancer’s unlimited growth. If DHX36 does affect telomerase the researchers will investigate ways to interfere with it, which may lead to new cancer therapies.

“Our research is aimed at blocking telomerase, which is responsible for the unlimited growth of 85-90% of cancers.

Because so many human cancers rely on telomerase to support their unlimited proliferation, it is a very promising target for the development of future anti-cancer drugs.”

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Treatment

The key cause of more than 80% of bowel cancers, beta-catenin has also been linked to breast cancer, melanoma and pancreatic cancer, among others. It also influences how dangerous the cancer will be – the more beta-catenin that accumulates in a cell’s nucleus, the more invasive the cancer. Beta-catenin contributes to cancer when it is inside the nucleus, where it activates a well-known cancer pathway. However, beta-catenin also does many essential tasks outside of the nucleus in normal cells such as anchoring the cellular scaffolding, so we need to find out how disruption of these different activities of the beta-catenin protein can lead to cancer formation.

Dr Henderson hopes to understand exactly how beta-catenin is transported within the cell. If he can find a way to prevent it moving into the nucleus, this will lead to new pathways which can be targeted by cancer therapies. Current therapies targeting beta-catenin only attempt to block it, with limited success. If Dr Henderson’s research is successful, they might find a way prevent it entering the nucleus in the first place and leading to cancer.

“Fundamental research takes time, but it really is the key to new discoveries and treatments. These grants are actually funding work that we started 11 or 12 years ago, but it’s really getting to an exciting stage now. We’re very grateful to Cancer Council NSW for their support.”

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Closer to a CLEAR understanding of what causes cancer

Data collection providing better care for an ageing population

Associate Professor Freddy Sitas, Cancer Research Division, Cancer Council NSW

Professor Emily Banks, The Sax Institute and National Centre for Epidemiology and Population Health, Australian National University

AIM: To establish a data and biobank resource for all adult cancers.

The CLEAR Study (NSW Cancer, Lifestyle and Evaluation of Risk), led by Associate Professor Freddy Sitas, was established in 2006. It is a population study of people who have recently been diagnosed with cancer that will help us understand the lifestyle and genetic factors that influence the disease in NSW. The first phase involves the collection of data from a range of cancer patients via questionnaires and blood samples in order to help researchers study the causes of cancer including genetic and environmental risk factors.

In August 2011, the first paper using CLEAR Study data was released. The results revealed that nearly half of those questioned did not understand what caused their cancer, and a quarter thought the disease could not be prevented. Yet we know that up to a third of all cancers can be prevented through lifestyle choices such as regular exercise, a healthy diet and quitting smoking. These findings have led to renewed calls for better health communication and policy.

“About 30 per cent of cancers can be prevented by making some really simple lifestyle choices. My big concern is that if the community is unsure about what causes the disease, people may not take the right steps to prevent it. People should also have access to their family history for hereditary conditions and make use of national cancer screening programs.”

If you would like to make a contribution to cancer research, contact the CLEAR study hotline on 1800 500 894 or email us at clear@nswcc.org.au. You can register and complete the information survey on line at www.clearstudy.org.au 11

survivorship

Photographer Belinda Pratten

survivorship

AIM: To answer questions about the causes and progression of cancer.

The 45 and Up Study is the largest study of healthy ageing ever undertaken in the Southern Hemisphere. Over 267,000 men and women aged 45 and over across NSW have been recruited and will have their health followed over the coming decades.

Led by Professor Emily Banks, the 45 and Up Study is a powerful resource for Cancer Council NSW, providing information about the causes of cancer and factors that increase an individual’s risk here in NSW. This means that researchers can study how, when, and why people get cancer, which will lead to better prevention and diagnosis. In addition, by comparing the 45 and Up Study with similar studies overseas, researchers can determine how cancer risk differs in Australia to the rest of the world.

Cancer Council NSW has already completed a number of statistical studies using data from the study, including colorectal cancer screening, cancer screening in migrants, smoking among migrants, social isolation among smokers, the infectious causes of nonmelanoma skin cancer, and how lifestyle affects prostate symptoms.

Cancer Council NSW is also working with The Sax Institute towards establishing Priority One, Australia’s world leading Biobank in the fight against chronic disease. This will store bloods from 45 and Up Study participants.

“The information collected by the 45 and Up Study will help researchers and policy makers gain a better understanding of how to provide the best possible care for a rapidly ageing population for conditions such as cancer, cardiovascular disease, arthritis, depression, Alzheimer’s disease and diabetes.”

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Research Title

13

Grant Type

Researcher

Institution

3 Years

A/Prof Tracy Bryan

Children’s Medical Research Institute, Wake Forest University

Project

3 Years

Dr Scott Cohen

Children’s Medical Research Institute, St Vincent’s Institute of Medical Research, CSIRO Molecular and Health Technologies

IGFBP-3 enhances autophagy to promote breast cancer cell survival during stress

Project

3 Years

Dr Sue Firth

Kolling Institute of Medical Research, University of Sydney

Novel regulation of beta-catenin intracellular transport and its role in cell polarity and migration

Project

3 Years

Dr Beric Henderson

Westmead Millenium Institute, Macquarie University

The mechanistic basis for prediction of response to alylating chemotherapy in high grade glioma patients by molecular markers of MGMT activity

Project

3 Years

Dr Megan Hitchins

University of NSW

A sting in the tail: focal adhesion targeting and mechanotransduction

Project

3 Years

Dr Geraldine O’Neill

The Children’s Hospital at Westmead, The University of Erlangen, University of Sydney

Activating a tumour supressor for leukaemia therapy

Project

3 Years

Dr Nicole Verrills

Lowy Cancer Research Centre, University of NSW, University of Newcastle

Mechanisms underlying impaired anti-EBV and antitumour immune responses in the absence of SAP

Project

3 Years

Dr Stuart Tangye

Garvan Institute of Medical Research

Mechanisms underpinning how brain cancer cells respond to drugs

Cancer Australia Priority-Driven Cancer Research Scheme (Pdccrs)

3 Years

Dr Kerrie McDonald

University of NSW, Peter MacCallum Cancer Centre, University of Melbourne

Risk and Prognostic Factors for Glioma in Australia

Cancer Australia Priority-Driven Cancer Research Scheme (Pdccrs)

3 Years

Dr Gianluca Severi

Royal Brisbane and Women’s Hospital, Royal Melbourne Hospital, Cancer Council Victoria, University of Melbourne, University of NSW, University of Western Australia

Phase III trial of Concurrent and Adjuvant Temozolomide chemotherapy in non-1p/19q nondeleted anaplastic glioma - The CATNON Intergroup Trial

Cancer Australia Priority-Driven Cancer Research Scheme (Pdccrs)

3 Years

Prof Anna Nowak

University of Western Australia

Using familial genetics to identify genes involved in the biology of Barrett’s Oesophagus

Innovator

1 Year

A/Prof Wayne Phillips

Peter Macallum Cancer Centre & University of Melbourne

Sentinel lymph node biospy in oesophageal adenocarcinoma - Improving staging accuracy and optimising treatment

Innovator

1 Year

Dr Sarah Thompson

The Royal Adelaide Hospital & University of Adelaide

Deep sequencing of glioma derived microparticles

Innovator

1 Year

Prof Georges Grau

Victor Chang Cardiac Research Institution & University of Sydney

Developing sphingosine kinase 2 inhibitors to block glioblastoma cell proliferation

Innovator

1 Year

Dr Anthony Don

Lowy Cancer Research Centre & University of NSW

Novel molecular targets for treatment of hepatocellular cancer (HCC)

Innovator

1 Year

Dr Lionel Hebbard & Prof Jacob George

University of Sydney & Westmead Millennium Institute

Discovering novel non-invasive diagnostic and prognostic markers in hepatocellular carcinoma

Innovator

1 Year

Dr Nicholas Shackel

Centenary Institute & Royal Prince Alfred Hospital

The role of imagable microspheres in radioembolisation treatment planning for HCC

Innovator

1 Year

Dr Kathy Willowson

University of Sydney

Pharmacogenomic approaches to minimise sorafenib toxicity in patients with liver cancer

Innovator

1 Year

Prof Michael Murray

University of Sydney

Randomised trial of endoscopic radiofrequency ablation versus complete mucosectomy with stent for Barrett’s high grade dysplasia or intramucoasl adenocarcinoma

Clinical Trials Protocol

1 Year

A/Prof. Reginald V.N. Lord

St Vincent’s Centre for Applied Medical Research, University of NSW

Involvement of helicase DHX36 in human telomere maintenace

Project

Structure and inhibition of the human telomerase enzyme complex

Duration

14

Research Expenditure

by Cancer Type Total $16.05M

All Cancers - $7,811,000

Other - $516,000

Pancreatic - $1,033,000

Oesophagus - $483,000

Brain - $854,000

Prostate - $437,000

Leukaemia - $826,000

Haematological - $314,000

Skin - $723,000

Lung - $249,000

Breast - $623,000

Neuroblastoma - $180,000

Colon/Colorectal - $596,000

Ovarian - $153,000

Cervical - $582,000

Non-Hodgkin’s lymphoma - $116,000

Liver - $558,000

Total - $16.05M

Would you like to help fund important cancer research?

Help us beat cancer by joining a research study If you are interested in taking part in a research study, you can register online at www.cancercouncil.com.au/joinastudy or call us for more information on (02) 9334 1398.

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For further information, visit www.cancercouncil.com.au and click on How you can help, or call our Donation Hotline on 1300 780 113.