Green Button Foundation donation to strengthen lymphoma research

With more than 6,000 people in Australia diagnosed each year, Lymphoma – a type of cancer that begins in the lymphatic system – has become the fifth most common cancer in Australia and the most common blood cancer.

There are more than 80 subtypes of Lymphoma, which are divided into two key categories: Non-Hodgkin Lymphoma and Hodgkin Lymphoma. With the incidence of lymphoma more than doubling in the last 20 years in Australia, vital research into this disease is more important than ever.

Thanks to a generous donation of $15,000 by The Green Button Foundation, research into lymphoma will be strengthened at the Olivia Newton-John Cancer Research Institute (ONJCRI), with the expansion of the Haematology Tissue Bank located at the Olivia Newton-John Cancer Centre to now include a dedicated Lymphoma Tissue Bank.

This means, tissue samples can be taken from consenting lymphoma patients for critical research, enabling ONJCRI clinician scientists and researchers to further understand the biology and nature of lymphoma and identify how the immune system responds to treatment.

Patients are embracing the opportunity to contribute to ONJCRI’s research efforts, with more than 40 people consenting to have their tissue stored for research within the first few months of the Lymphoma Tissue Bank’s commencement.

A/Prof Eliza Hawkes is a National Health and Medical Research Council (NHMRC) Research Fellow at ONJCRI and Lymphoma Lead and Medical Oncologist at Austin Health. A/Prof Hawkes says, “Using samples from the Lymphoma Tissue Bank, we can quickly identify unusual features of the cancer, then go back to see how it behaved in our patients, to better understand a path forward to better outcomes.”

“The development of a dedicated lymphoma tissue bank located within ONJCRI – only possible with The Green Button Foundation's generous support – brings patient-focused research full circle and highlights that clinical practice and research are not distinct entities,” she says.

Tissue samples can offer rich insights into lymphoma development and can provide information about which targeted therapies may be most effective for each patient. As researchers learn more about the changes in cells that cause cancer, they can continue to develop new drugs or treatments that specifically target these changes.

Says A/Prof Hawkes, “The Lymphoma Tissue Bank is a fantastic example of the amalgamation of efforts of generous donors, patients who participate in local research efforts, clinicians and researchers, and perfectly showcases what we can achieve by having research institutions embedded within the hospital setting.”

The ONJCRI is extremely grateful for the generous support of The Green Button Foundation.

 

Image description:

Reed-Sternberg cell; photograph shows normal lymphocytes compared with a Reed-Sternberg cell. Reed-Sternberg cell. Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. These cells are found in Hodgkin lymphoma.

Image source and creator: National Cancer Institute


Taking science to the next generation

For 25 year old, Shalini Guleria, science presents a world of curiosity and opportunity. It is this outlook that has led her to the position of PhD candidate at ONJCRI, while also pursuing ways to bring the magic of science to young children.

At the ONJCRI, Shalini’s research is focused on understanding the role of adipose tissue, or fat, in mammary gland development and also in breast cancer progression.

As part of the Cancer Single Cell Genomics Laboratory, Shalini explains that she is, “using a range of innovative techniques to explore this area and understand the underlying mechanisms in relation to cancer”.

As well as completing her PhD, Shalini is also the founder of a social enterprise called Science Box, which started in late 2018 in New Zealand. The aim of Science Box is to empower children to be involved in science.

“I know that there are so many children out there aged between 5 and 12 who fear science,” says Shalini.

“This was confirmed when I heard a young girl say science was too hard, mostly for boys and you had to be super clever to do it,” she said.

Her vision is to empower children of all ages, socioeconomic backgrounds and demographics to enjoy the magic of science. Science Box aims to explore different science concepts in engaging ways while using household items.

In recognition of her outstanding achievements, Shalini was recently named one of New Zealand’s YWCA’s Y25: 25 women, 25 years and under, doing incredible things. The YWCA describe these women as some of the most inspirational young women, including some truly exciting, dynamic forces in the start-up scene.

“This is an incredible honour to be recognised amongst some trail blazing young women and also a big acknowledgement to my team at Science Box for their continual support,” said Shalini.

Shalini’s PhD supervisor and Head of the Cancer Single Cell Genomics Laboratory, Dr Bhupinder Pal says, “It is inspiring to see Shalini use her research expertise and love of science to encourage a new generation. We are all incredibly excited for Shalini on receiving this recognition”.

So, where to from here? Shalini says, “apart from completing my PhD and using my research to make a difference for people with breast cancer, I also want to make an impact on STEM education by taking Science Box global!”

Given all that Shalini has achieved already, it is not hard to believe that these goals will indeed become a reality.

Congratulations Shalini, on this well deserved recognition.

Find out more about Science Box https://www.sciencebox.co.nz


Cancer research and charity are all in a day’s work

As a former international student, Pat Thilakasiri – a researcher in the Cancer Therapeutics Development Group at the Olivia Newton-John Cancer Research Institute (ONJCRI) - knows all too well what it’s like to move far away from family and friends to study in a new country.

Many international students leave their usual support networks behind to follow their dream of studying abroad. Many need to undertake part-time or casual work to support themselves while on a student visa.

When news broke of the Coronavirus pandemic, Pat had an inkling that international students would be seriously impacted, so he quickly began to prepare a strategy to support those he thought would be in need.

“With the threat of mass job losses, and without Australian citizenship, I knew early on that many international students would not have money for food, medical or legal assistance, and I knew they would not be eligible for government assistance,” he said.

Pat reached out to his network on Facebook and after a rush of offers to help, on 29 March 2020 he was able to send out his first lot of food packages, containing grocery items that would last for up to two weeks.

“Lockdown meant that many people lost their jobs. There was a group of people that no-one could seem to help – international students. They didn’t have money to pay rent or feed themselves. They were in deep trouble, they were on their own, and we needed to help them,” says Pat.

Pat’s ‘food bag’ initiative for international students has since spread to all the states and territories around Australia (there are groups in each state and territory to coordinate) with some international groups following suit.

So far, Pat estimates they have helped around 3,000 international students across Australia, with the majority located in Victoria and New South Wales. Pat and his supporters are still packing food bags from four distribution centres around Victoria that they have set up.

This isn’t the first time Pat has helped those in need. He coordinated similar projects for people affected by the Boxing Day tsunami in 2004, devastating floods, and for individuals needing housing, or school books.

So, how does he juggle all of this with his full-time job as a scientist at ONJCRI (plus a weekly volunteer job as radio show host on a community radio station)? It’s all about time management, he says. It’s done outside of working hours and he has a lot of people to help him.

“All of us come together. People have donated a lot of food, housing and professional services for these students, including doctors, psychologists and lawyers, who have provided their services free of charge. No money is collected or exchanged – it’s all about providing food and services.”

Pat is working on gastric and breast cancer projects at ONJCRI and, along with his team, is repurposing a drug, Bazedoxifene, and its analogues to treat cancers by targeting the JAK STAT3 pathway (a chain of interactions between proteins in a cell which is involved in processes such as immunity, cell division, cell death and tumour formation).

In addition to this important research, it’s clear that charity is also a huge part of Pat’s life.

“I think as a human you should always help other people. It is our ultimate duty to help whoever is in trouble. In this case, Coronavirus doesn’t distinguish whether you are white, whether you are from Sri Lanka, whether you are rich or poor. It’s simple - when people are in need, people should help each other.”


Early access to new National Drug Discovery Centre

ONJCRI Director, Prof Matthias Ernst has been named as one of two inaugural recipients of subsidised access to the newly opened National Drug Discovery Centre (NDDC) at the Walter and Eliza Hall Institute of Medical Research.  The NDDC has been established to offer researchers in Australia access to state-of-the-art high-throughput screening to fast track the discovery and development of new medicines, so patients can benefit sooner.

The announcement was made on Thursday 12 March by Federal Health Minister the Hon Greg Hunt MP and Victorian Health Minister the Hon Jenny Mikakos MP at the opening of the NDDC.

This significant investment will enable Prof Ernst, and his team, to progress their pivotal work that aims to uncover how to make cancer more visible to the immune system and enhance the effect of anti-tumour immune therapies.

“We will identify lead compounds to inhibit a molecule in immune cells that otherwise suppresses the capacity of a patient’s immune system to kill cancer cells,” he said.

“Once these lead compounds have been identified, they provide a starting point to develop novel drugs and to test their efficacy in treating breast, bowel, pancreatic and other solid tumours”.

The announcement provides an exciting opportunity for Prof Ernst and his team to focus on scientific advances in cancer immunotherapy.

“Ultimately, these findings would serve as a starting point for the development of new anti-cancer drugs that could treat breast, bowel, pancreatic and other solid tumours,” Professor Ernst said.

Congratulations also to A/Prof Anthony Don, from the University of Sydney and Centenary Institute who was announced as the other NDDC recipient. A/Prof Don will, who will lead a project to develop new drugs that reverse systemic insulin resistance that causes type 2 diabetes.


Study reveals that gene knockout can combat obesity

Prof John Mariadason

In what started as a research project into colon cancer, has resulted in a major discovery that could lead to a new treatment for obesity. The study, undertaken at the Olivia Newton-John Cancer Research Institute (ONJCRI) and recently published in Nature Communications, has found that inactivating a gene called HDAC3 specifically in the intestine could protect people from diet-induced obesity.

Obesity, and eating high fat diets increases the risk of developing several types of cancer, including colon cancer. The findings from this study may therefore provide hope for some of the 12.5 million Australian adults who are overweight or obese, while also reducing their cancer risk.

In 2014, Prof John Mariadason, Head of the Gastrointestinal Cancer Program at ONJCRI, began a research study looking at the function of a specific set of proteins called histone deacetylases or HDACs in colon cancer. There are 10 HDAC genes within our bodies, and drugs targeting these proteins are currently used to treat blood cancers.

This pre-clinical study originally aimed to assess if these drugs could also be repurposed for treating colon cancer. As part of this study the researchers inactivated the HDAC3 gene in the intestine and colon of mice to assess its impact on colon cancer development.  During these studies the researchers made the remarkable finding that these mice were protected against obesity.

The normal job of the intestine is to absorb nutrients including lipids or fats, and then move these into the liver.  However, the researchers discovered that when HDAC3 is knocked out, the cells in the intestine start doing an additional job – they break down the lipids within the intestinal cells themselves.  This results in less lipid being available for uptake into the body, and ultimately, over time, in a reduction in weight gain.

On identifying this impact, Prof Mariadason expanded the study with Prof Matthew Watt, Head of Department of Physiology, School of Biomedical Sciences at the University of Melbourne; and Prof Andrew Scott, Head, Tumour Targeting Program ONJCRI, Director, Department Of Molecular Imaging And Therapy, Austin Health. It was found that mice that were fed a high fat diet, which is typical for people with diet-inducted obesity, had a significant reduction in body weight in as little as three months.

‘We have found that there is a new role for the HDAC3 gene in the breakdown of fats,’ said Prof Mariadason.

‘We know that obesity is linked to cancer and if we can block this particular gene then we could protect people from diet-induced obesity and a new obesity treatment could be delivered,’ he said.

The next phase of the obesity treatment study will focus on the delivery of HDAC3 targeting drugs specifically to the intestine, as most drugs are absorbed into the whole body rather than just one specific part.

Prof Mariadason explains, ‘We will now look for opportunities to package the drug differently so it can be delivered directly to the intestine including with the use of nanoparticles.’

The colon cancer study has also continued and findings are expected to be released in the next six months.

 

Publication details:

Dávalos-Salas, M., Montgomery, M.K., Reehorst, C.M. et al. Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity. Nat Commun 10, 5291 (2019). 

 


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.