Prof Andrew Scott to lead national brain cancer study

Health Minister Greg Hunt has announced Prof Andrew Scott, from La Trobe University’s School of Cancer Medicine and the Olivia Newton-John Cancer Research Institute, and Austin Health, will receive $1,520,000 over five years from the Medical Research Future Fund (MRFF) to run a clinical trial involving patients with high-grade glioma or glioblastoma (GBM).

The MRFF supports Australia’s brightest medical researchers in their fight against rare cancers and rare diseases.

Prof Scott said his multi-centre study would bring together 19 investigators from major hospitals and universities around Australia and will investigate the role of FET-PET imaging technology in the treatment of GBM patients.

“Currently only 25 per cent of patients with GBM are still alive two years after diagnosis and just 10 per cent live for 5 years, despite receiving treatment,” Professor Scott said.

“New imaging techniques that incorporate prognostic information are required to improve patient outcomes by individualising patient care. Our trial will investigate how we can use the FET-PET technology to provide more accurate treatment and improve survival rates.”

La Trobe Deputy Vice Chancellor (Research) Keith Nugent congratulated Professor Scott.

“La Trobe and ONJCRI are committed to working together to transform the lives of cancer patients. Andrew Scott is a leader in his field and this grant will allow him to lead important research.”

The Health Minister has also announced that Professor Scott will be a member of the Strategic Advisory Group that will support the $100 million Australian Brain Cancer Mission.

The Mission is a partnership between the Federal Government, philanthropists, medical experts, patients and their families. Its aim is to double survival rates for people living with brain cancer over the next 10 years.


Clinical Trial of Anti-EphA3 Antibody Enrolls First Brain Cancer Patient

Clinical trialing of a drug which promises to deliver new hope for people with the most common and lethal form of brain cancer – glioblastoma – has begun at the Olivia Newton-John Cancer Research Institute (ONJCRI).

KB004 (Ifabotuzumab), a drug developed by leading Australian doctors and scientists, represents an exciting new approach in the treatment of brain cancers by targeting a protein on the cancer cells called EphA3.

The drug has already been shown to be safe and have potential benefits in the treatment of leukaemia. This new trial represents a major step towards tackling brain cancer, which has a stagnant and unacceptably low survival rate and takes the lives of over 1200 Australians every year.

The study will take place at Austin Health (Olivia Newton-John Cancer Centre) and Royal Brisbane and Women’s Hospital. This clinical trial was made possible by a grant of $500,000 from Cure Brain Cancer Foundation, and was awarded following a competitive process. The drug is provided by Humanigen, a U.S. biotech company based in the San Francisco area.

‘This study gives hope to patients with glioblastoma, which is the most common form of adult brain cancer and one with a terrible prognosis,’ said A/Prof Hui Gan, who will lead the trial at ONJCRI.

‘This is the first EphA3-targeting drug for glioblastoma, and represents an exciting new approach to the treatment of brain tumour patients. It also shows the power of what can be achieved by close collaboration between doctors, scientists, pharmaceutical companies and philanthropy.’

KB004 (Ifabotuzumab) was created as the result of a collaboration between Prof Andrew Scott (ONJCRI), Professor Andrew Boyd, (QIMR Berghofer) the late Professor Martin Lackmann (Monash University), and subsequently with US company Humanigen.

'Collaboration is key to meeting the challenge of brain cancer. This cancer kills more children in Australia than any other disease and more people under 40 than any other cancer,’ Associate Professor Gan said. ‘It is our mission to help people live better with cancer and defeat it, and we are optimistic that KB004 can help us achieve that.’

'The need for more effective treatments for glioblastoma is starkly apparent', Michelle Stewart, CEO Cure Brain Cancer Foundation said. 'This trial is an important step towards finding effective treatment for people living with brain cancer. Cure Brain Cancer Foundation is proud to support this innovative Australian research.'


ONJCRI awarded over $4M for cancer research

The Olivia Newton-John Cancer Research Institute (ONJCRI) has been awarded more than $4 million in this year’s National Health and Medical Research Council (NHMRC) Project Grant Scheme, announced this week by the Federal Minister for Health, the Hon Greg Hunt.

The money will be used to fund research into lung cancer, colorectal cancer, stomach cancer, lymphoma, antibody therapies and immunotherapies.

We are incredibly proud of our researchers. For the third year running, they have had a 25% success rate in securing NHMRC grants, against a national average of 16.4%.  It speaks to the quality of work conducted at ONJCRI, and the recognition of this work among our peers.

PROJECT GRANTS

Associate Professor Alexander Dobrovic, 'Using chromosome rearrangements as tumour-specific markers for disease monitoring in lung cancer using droplet digital PCR', $1,081,334.80

There are no useful markers, apart from CT scans, to determine the effectiveness of therapy in patients with lung cancer. This study will assess highly sensitive methods based on liquid biopsies and whole genome sequencing that can monitor the blood to determine whether DNA from the patient’s tumour is present. This will allow clinicians to modify therapies to better manage the cancer.

Dr Amardeep Dhillon, 'Transcriptional Effectors of Oncogenic ERK Signaling in Colorectal Cancer', $820,776

This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. The research team expects to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.

Dr Michael Buchert, 'Exploiting the cross talk between Tuft cells and group 2 innate lymphoid cells for tissue homeostasis and disease', $831,162

The project investigates the cell-to-cell communication between rare epithelial cells called tuft cells and group 2 innate lymphoid cells (ILC2) whose role is to protect the stomach from infections with parasites. Surprisingly however, in the context of chronic inflammation of the stomach, called gastritis, and during early stages of stomach cancer the abundance of these two cell types dramatically increases but by interrupting their line of the communication, inflammation and cancer progression can be partially alleviated and reversed.  The aim of this project is to identify the mechanisms by which the communication between tuft cells and ILC2s is hijacked to promote gastric disease and this knowledge may help to develop strategies to combat stomach cancer.

Prof Andrew Scott, 'Alpha Particle Therapy of Solid Tumours', $715,005

Antibody therapeutics are achieving major clinical success in a range of cancers, however many patients do not respond to this type of treatment or eventually become unresponsive. This project will explore the use of potent alpha particles linked to antibodies that target tumours throughout the body, thus creating a new approach to treating advanced cancer.

EARLY CAREER FELLOWSHIP SCHEME

Dr Eliza Hawkes, 'Biomarker-driven applications of immunotherapy in lymphoma', $189,384

Lymphoma is the sixth most common cancer. Most patients who are diagnosed with lymphoma are aged over 50 and between 30 and 50 per cent will die from the disease. Immunotherapy has emerged as a possible new treatment for lymphoma. Based at the world-renowned Olivia Newton-John Cancer Research Institute, Dr Eliza Hawkes will conduct a series of trials to evaluate the use of immunotherapy in lymphoma and develop better use of immunotherapy strategies for treating three key lymphoma subtypes.

Dr Miles Andrews, 'Deriving actionable strategies to enhance cancer immunotherapy response', $438,768

Many cancer treatment outcomes have improved in recent years with the development of effective anti-cancer immunotherapy. However, an overwhelming majority of patients are yet to benefit from this form of treatment. A better understanding of the reasons why not all cancer patients respond to immunotherapy is needed in order to extend the benefits to a greater number of patients. Dr Miles Andrews will investigate several distinct aspects of anti-tumour immunity to identify new biomarkers and ways to improve therapeutic options involving these anti-cancer agents.

 


Colon cancer finding moves lab closer to new treatments

Prof John Mariadason

With more than 4,000 people dying from colon, or bowel, cancer in Australia each year, there is an urgent need to develop new treatments for this disease. Which is why Prof John Mariadason is excited about finding potential new ways of managing colon cancer.

After 15 years of research his team has homed in on a family of proteins that are required for the growth of colon cancer – and found a way to block them.

They have shown that combining drugs that target proteins called histone deacetylases with drugs that block a second pathway called MAPK, stops the cancer in its tracks; preventing the ability of the cancer cells to grow and move, and even causing their death. (A pathway is a series of actions among molecules in a cell that leads to a certain product or a change in a cell.)

“We are extremely excited by this finding as it could represent a new way of managing colon cancer. We hope that this discovery will rapidly lead to a clinical trial, aimed at stopping the spread of colon cancers around the body,” he says.

Battle against colon cancer advances on several fronts

John’s Oncogenic Transcription Laboratory, which comprises scientists, clinicians and students doing PhDs, is also involved in conducting pre-clinical work trialling newly developed drugs or drugs which are showing activity in other cancers.

They test each drug on 80 genetic versions of colon cancer nurtured in the lab. “They’re our workhorses, our tools,” he says.

By identifying which colon cancer cell lines respond best to a given drug, the researchers hope to tell oncologists which ones may provide benefits to individual patients, tailoring treatment to the needs of these patients.

John's team is particularly interested in “epigenetic therapy”. The rapidly advancing field of epigenetics – non-genetic influences on the ways genes are expressed – is revolutionising cancer research by looking beyond the inherited mutations that cause cancer.

His team has shown that another family of proteins, bromodomain-containing proteins, is required for colon cancer growth, and demonstrated that drugs targeting them block the growth and cause death of colon cancer cells. The researchers have advanced understanding into why these drugs work more effectively in some cancers than others, using this knowledge to develop novel therapeutic combinations.

 

 


New cancer imaging centre to shine a light on the life of a tumour

A $2 million grant from the Australian Cancer Research Foundation (ACRF), announced today, will fund a state-of-the-art imaging centre to understand how and why tumours corrupt the normal cells of their immediate environment.

The grant enables the Olivia Newton-John Cancer Research Institute (ONJCRI) and La Trobe Institute of Molecular Science (LIMS) to extend its ground-breaking work on the interaction between individual tumour cells and normal cells, and accelerate the speed with which results in the laboratory can be translated into treatments for cancer patients.

‘Cellular interactions are crucial for tumours – they drive the growth of tumours and their spread to metastatic sites; these interactions are also often responsible for tumours becoming resistant to targeted therapy,’ Prof Matthias Ernst, Scientific Director of ONJCRI, said. ‘This new centre will literally shine a light on what happens in the micro-environment around a tumour, giving us the information we need to develop effective, targeted anti-cancer therapies.’

‘We know that tumour cells coerce and corrupt their environment to their advantage. If we understand the interactions and mechanisms they use to do this, we will better understand how to counter them.’

Prof Ernst, who is also the Head of the School of Cancer Medicine at La Trobe University, welcomed the generous support of the ACRF.

‘Australia is blessed with world-class cancer research and is playing a lead in the development of anti-tumour treatment, including those that harness the power of the body’s own immune system. We all recognise that our research achievements have to stay abreast of the rising rates of cancer, and the new ACRF Centre for Imaging the Tumour Environment will facilitate that.’

‘The ACRF Centre for Imaging the Tumour Microenvironment will offer cutting edge capabilities for researchers both at the ONJCRI and at LIMS who are studying the interactions between cancer cells. The collaborative opportunities that will arise from the centre will also greatly benefit advances in cancer research,’ said Professor Andrew Hill, Head of La Trobe University’s Institute for Molecular Sciences.

‘The ACRF Centre for Imaging the Tumour Environment will provide new insights into how the micro-environment impacts tumour growth, leading to new targeted and immune based cancer treatments that will benefit all Australian cancer patients,’ ACRF Chief Executive, Professor Ian Brown, said.

‘Thanks to the generosity of our many supporters from around Australia we are able to award high-impact grants, allowing Australia’s best scientists to embark on ground-breaking research projects. These cancer research initiatives cover all types of cancer and speed up discoveries, ultimately working to save lives by saving time,’ says Professor Brown.

Each year ACRF challenges the Australian cancer research community to propose projects that are bold and have the potential to make a significant impact on cancer prevention, detection and treatment.

In 2017, thirteen projects were submitted from across the country and evaluated by ACRF’s esteemed Medical Research Advisory Committee. The Committee recommended four grants to the ACRF Board for projects that have the greatest potential to change treatment outcomes for all Australian cancer patients.


New computing tool points to novel cancer therapies

Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI) have developed computing tools to investigate the activity of microRNAs – tiny strands of genetic material that play a key role in regulating cancer cell survival.

They have used the tools to demonstrate that one microRNA plays a key role in regulating the growth and movement of melanoma cells.

In creating the computer-based model, the researchers paved the way for the identification of other microRNAs that potentially pose suitable targets for a new generation of cancer therapeutics.

Most of us have heard of DNA and the ‘genetic code’ that makes every living thing unique, but equally as important is RNA. RNA is the ‘messenger’ molecule carrying genetic information stored in DNA out to the tiny factories within cells where this information is decoded and ‘translated’ into proteins.

MicroRNAs are very short strands of RNA that play a vital role interacting with their longer protein-coding ‘messenger RNA’ cousins, and fine-tuning the decoding process. Typically, microRNAs do this by binding to specific messenger RNA molecules, preventing them from being ‘readable’ by the protein-building machinery.

Tiny molecules, vital role in cancer cell survival

MicroRNA molecules have been found to be key regulators of cancer cell behaviour by altering the balance of pro- and anti-cancer protein formation. But cancer cells can take control of microRNAs, using them to support the production of a protein repertoire that fuels cancer cell survival. 

The interactions between the tens of thousands of microRNA and messenger RNA molecules that float around within any single cell are difficult to study. Until recently there were few tools to fathom this complexity and accurately predict which microRNAs interact with which messenger RNAs, and what this means.

Researchers in the Institute’s Cancer Immunobiology Program and the Systems Biology Laboratory at the University of Melbourne developed computing tools to identify novel potential interactions between these molecules and to then assess their functional significance. The methods work by simultaneously modelling the abundances of microRNAs with those of messenger RNAs, whilst taking into account functional read-outs of what the cancer cells are doing.

Tool may identify other new cancer targets

The researchers used the tools in 2016 to demonstrate that the microRNA miR-29b-3p played a key role in regulating the invasiveness of melanoma cells.

“We showed the methodology can be used to identify microRNAs and their target messenger RNAs that have direct relevance to cancer cell function, opening the door to investigating other microRNAs that could potentially be novel cancer therapeutic targets,” Dr Miles Andrews, ONJCRI Clinician Scientist says.

 


Taking on aggressive breast cancer with non-cancer drugs

A very aggressive type of breast cancer that is hard to treat with standard chemotherapy may respond to treatment with drugs already used for inflammatory diseases like rheumatoid arthritis.

Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI) hope some of these drugs may provide alternatives to the current treatments, and may also have less side-effects. Such drugs may also have the added benefit of allowing doctors to treat patients sooner, because these drugs have already passed clinical trials for other diseases.

Inflammatory breast cancer is relatively uncommon but it’s the most aggressive form of breast cancer you can get. By the time most patients are diagnosed the cancer is often at an advanced stage. Sadly, there is a less than 40 per cent chance of surviving five years.

ONJCRI Scientific Director Prof Matthias Ernst says, “Because inflammatory breast cancer is an uncommon disease the pharmaceutical companies have less resources to develop new treatments. But more research is critical to find better treatments for patients and we are committed to continuing this important work”.

Prof Ernst’s team in the Cancer and Inflammation Program have made it one of their missions to focus on the disease and are making some exciting discoveries, which the team expects to be published next year.

The team is exploring the role of what are called inflammatory cytokines. Cytokines serve as messengers to activate cells to respond in various ways. In this case, damaged cells release cytokines to warn the immune system of an ‘emergency’ in the body, triggering the process of inflammation.

They are examining the relationship between a particular cytokine and tumour subclones of the cancer.

“Cancer cells aren’t all the same,” Prof Ernst explains. “There are different sets of mutations in different clones that together make up the whole cancer. Some clones are fast-growing, others are slow. Our hypothesis is that a fast-growing clone can help a slow-growing one to grow faster and perhaps become more aggressive. We want to know if this cytokine is the trigger.”

Prof Ernst’s says the team’s ultimate goal is to see whether their findings in preclinical models hold true in human trials.

“The exciting thing is that many cytokines can be easily neutralised with drugs that are already used to treat other inflammatory diseases like rheumatoid arthritis,” he says.

“If we can prove that some of these existing drugs provide a novel treatment for inflammatory breast cancer, we could begin treating patients with them more quickly than it would take to conduct clinical trials on a new drug.”

An added benefit is that some anti-cytokine drugs could potentially also help to overcome the tumour’s resistance to treatment and reduce the side effects associated with existing treatments.


New test may streamline colon cancer treatment  

Colon or bowel cancer is the second most common cancer in Australia, with more than 16,000 cases diagnosed each year. A standard treatment for bowel cancer is a drug called Avastin, but unfortunately it doesn't work for all patients.

Olivia Newton-John Cancer Research Institute (ONJCRI) researchers have developed a new test that may help streamline treatment for colon cancer patients by predicting whether or not they will respond to Avastin. The test would help doctors tailor treatments for individual patients and spare those patients who may benefit from the drug any side effects.

The researchers have developed what’s called a ‘biomarker’ (biological marker) that predicts whether patients will respond to the drug Avastin. Avastin works by slowing the growth of new blood vessels needed by cancer tumours to grow.

Previously, no test existed to predict whether people with the cancer would respond to the treatment or not.

“This classification test is not yet widely available in the clinic, and more testing is required to confirm these results, but nevertheless these are exciting and positive findings that could potentially change the way we select treatment for colon cancer patients in the near future,” says Dr Jennifer Mooi, medical oncologist and researcher.

Findings aired at international conference

Jennifer recently presented the findings at the European Society for Medical Oncology Congress in Madrid, Spain, which attracted around 23,000 oncology health professionals.

They were made after analysing more than 300 tumour samples from patients previously involved in the ‘MAX clinical trial’, led by Associate Professor Niall Tebbutt, who directs the Medical Oncology Unit at Austin Health. Professor Tebbutt works closely with Prof John Mariadason, Head of ONJCRI’s Oncogenic Transcription Laboratory.

Recent studies have shown that colon cancer can be divided into four “molecular subgroups” according to patterns of genes expressed in the tumour. Our research team showed that by classifying patients’ tumours in this way, two out of the four molecular subgroups of colorectal cancer respond better to Avastin.

Study part of laboratory’s drive to personalise cancer treatment

“At the moment, Avastin is given to all colon cancer patients but only a subset of patients benefits from it,” John says. “Our findings of this potential biomarker are exciting – it means we are closer to being able to select therapies more specifically for a patient with colon cancer. This will help doctors tailor treatments that are most likely to work for a particular patient and spare them from unnecessary toxicities of treatments that are unlikely to work for their cancer,” he says.

This research was sponsored by the Australian Gastrointestinal Trials Group (AGITG) and a grant from the National Health & Medical Research Council jointly awarded to John and Niall.

 


Melanoma investigations point to new drug

Dr Erinna Lee

Melanoma is the third most common cancer in Australian men and women - and a wily opponent for researchers like Olivia Newton-John Cancer Research Institute's (ONJCRI) Dr Erinna Lee, a Postdoctoral research fellow in the Cell Death and Survival Laboratory.

Significant advances have been made into treating melanoma but unfortunately not all patients respond to the treatments available. Erinna and her colleagues are making inroads into finding new drugs to help these patients.

The researchers are tackling a family of proteins implicated in melanoma, called BCL-2, which act to keep the cancers alive. BCL-2 proteins are essential for determining the survival of all cells but when this process goes awry they can also contribute to the development of cancer.

“We’re starting to realise that melanoma may in fact be clever enough to escape chemotherapy-induced cell death by relying on a larger repertoire of pro-survival BCL-2 proteins for survival,” says Erinna.

“Our research in vitro and in animal models has recently shown that a more robust combination of drugs might be required. We are now looking at different combinations of drugs that will be able to kill melanoma more aggressively,” she says.

The researchers, working in the Cell Death and Survival Laboratory, have developed novel compounds that can specifically target certain BCL-2 family members and neutralise their pro-survival activity in cells.

Drug combinations the key to killing melanoma

The scientists have used the compounds to show that the inactivation of two proteins – called MCL-1 and BFL-1 – kills melanoma cells relatively well. A new drug acting against MCL-1 has been developed elsewhere but there is still no drug available against BFL-1.

Erinna says that based on current results, the researchers now believe that a drug targeting BFL-1 could be highly effective for treatment of melanoma, particularly if used in combination with the currently available MCL-1-targeting molecule.

Approach may work with other cancers

The researchers will use their findings to focus on developing drugs in the future that work against BCL-2 proteins for potential treatments.

Additionally, the compound they have developed allows them to profile other cancer types and see if they are dependent on BFL-1 for their survival. The scientists hope that using this approach could identify other cancer patients for which a BFL-1-specific drug could be useful if, and when, it is developed.

Some of the work involved researchers at the Walter Eliza Hall Institute. More findings are expected in late 2017 or early 2018.


Tackling triple negative breast cancer on two fronts

Dr Normand Pouliot

Triple negative breast cancer patients - often young women - cannot be treated with anti-oestrogen drugs like patients with other forms of breast cancer. Scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) are investigating ways to make this cancer more treatable with a test to identify patients earlier and a drug derived from snake venom.

"I think this research could make a significant impact in terms of being able to treat patients that can't be treated now." says Dr Normand Pouliot Head of the Matrix Microenvironment and Metastasis Laboratory.

Most women diagnosed with early breast cancer can be treated successfully thanks to modern therapies including anti-oestrogen drugs. Unfortunately, for those with triple negative breast cancer (TNBC), anti-oestrogen drugs are not an option.

Unlike other cancers, TNBC cells lack three surface receptors normally targeted in treatment, one of them an oestrogen receptor. Normand and his Laboratory colleagues are working on converting TNBC to a subtype of cancer that expresses the oestrogen receptor so it can be targeted by existing anti-oestrogen drugs.

Proteins may predict metastases risk

Currently, patients who will develop metastases cannot be predicted. Part of the research is aimed at developing a new prognostic ‘biomarker’ – proteins present in the cancer that identify TNBC patients at high risk of metastasis (development of secondary tumours).

The researchers are analysing cancer tissues from a group of TNBC patients looking for two proteins that interact to control the movement of cancer cells in distant organs. The presence of these two proteins indicates that some patients are more likely to develop metastases.

“If both are expressed in the cancer we know that we have to check that patient very carefully because they’re more likely to progress to metastases,” Normand says.

Snake venom may lead to safe, effective treatment

The other main thrust of the research is the development of a new drug derived from snake venom.

The scientists are investigating using a protein found in snake venom to create an inhibitor. It is hoped the inhibitor will stop TNBC cells spreading to other parts of the body as well as making them treatable with anti-oestrogen drugs.

“When we treat people with this inhibitor we want to know if we block metastases, and if we increase the response to anti-oestrogen because we induced the expression of oestrogen receptors,” Normand says.

“It’s a double whammy on the cancer cells – you block their ability to spread to distant organs and you also make them responsive to anti-oestrogen drugs. The attractive aspect of this is that anti-oestrogens are already being used in the clinic and are relatively safe.”