A Newcastle-led research team, backed by national and international experts, is forging ahead in its mission to develop a life-saving treatment for the most aggressive and lethal of brain cancers – high grade gliomas (HGG), following the announcement of an $18.7 million Australian Government grant.
The team, led by University of Newcastle Professor Matt Dun*, of HMRI's** Precision Medicine Research Program, will test a suite of new, next-generation therapies it has developed, including drugs designed to overcome the blood-brain barrier. The aim is to reach clinical trials within five years, offering renewed hope to patients and families where none currently exists.
The $18.7m grant is provided through the Frontier Health and Medical Research initiative, via the Australian Government's Medical Research Future Fund (MRFF). The Frontier initiative will provide $700 million over 10 years to support research that delivers a 'moonshot' by creating a treatment for a currently serious and incurable health condition.
High grade gliomas (HGG) are one of the deadliest brain cancers, striking more than 2,000 Australians every year.
In children, the most common form of HGG is diffuse intrinsic pontine glioma (DIPG), a devastating diagnosis, with most children surviving less than 12 months, even with radiotherapy. In adults, glioblastoma accounts for 65 per cent of all brain cancer deaths and still has no effective treatment.
High grade gliomas, including DIPG and glioblastoma, are hard to treat because:
- They grow in very sensitive parts of the brain, making it difficult to remove.
- Typical chemotherapies do not provide a benefit because they do not penetrate the blood-brain barrier (a protective shield around the brain).
- The tumours have complex genetic and immunological features that make them hard to target.
Professor Dun and his team have identified a critical gene that drives the growth and survival of HGGs.
Their research has shown that blocking this gene with new brain-penetrant drugs, especially when combined with radiotherapy and targeted therapy, can extend survival in preclinical models by more than 150 per cent.
"Now, we've developed a suite of next-generation therapies designed specifically to reach the brain and target the tumour," Professor Dun said.
"Our mission is to bring one of these new treatments to clinical trials within the next five years and bring hope to people who currently have no options."
Despite decades of research, Professor Dun said therapeutic progress to treat HGGs had been minimal, largely due to the challenges of delivering drugs into the brain and the complex biology of these tumours.
"Our research directly addresses these barriers by developing novel, brain-penetrant therapies that target dependencies of these cancers.
"By advancing both a lead therapy and an additional, similar treatment, we're building a robust, adaptable pipeline with real potential to improve patient outcomes, offering hope, where currently none exist."
Relentless research: A future for all families facing brain cancer
In 2018, Professor Dun's two-year-old daughter Josephine was diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) – an incurable childhood brain cancer.
Through genetic sequencing of Josephine's tumour and an extensive literature review, Professor Dun and his team identified genes critical for DIPG survival, and a combination of drugs to target the tumour.
Josephine was the first child in the world given a new therapy called paxalisib that slowed the tumour's growth and gave her another year of life. Sadly, she passed away in December 2019, 22 months after her diagnosis.
"This grant holds particular significance for me, as it builds on the research we began in response to my daughter's diagnosis," Professor Dun said.
"But it's not just personal, it matters to the patients, families, clinicians, researchers, and charities, who have been working for years to change the outlook for one of the most underfunded and devastating cancers globally. For too long, people diagnosed with high-grade glioma, both children and adults, have been met with a sense of hopelessness. This funding represents a turning point."
Team science at its best
University of Newcastle Vice-Chancellor, Professor Alex Zelinsky AO, said the University was honoured to lead the initiative.
"The University of Newcastle is immensely proud to be leading this project, which epitomises the very best of university research – bold, collaborative, and focused on real-world outcomes for patients and families.
"This significant investment recognises the extraordinary dedication of Professor Dun and his team, whose work is pushing the boundaries of science to deliver hope where none has existed."
Professor Dun said the strength of collaboration behind the funding made it even more powerful.
A national and international network of leading researchers, clinicians, and translational experts has been established through partnerships with the University of New South Wales, Children's Cancer Institute, Stanford University, University of Queensland, University of Adelaide, University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital, University of Sydney, Liverpool Hospital, North Shore Private Hospital and John Hunter Hospital.
"This is team science at its best, and it's precisely what's needed to take on one of medicine's most complex and deadly challenges," Professor Dun said.
"Neil Armstrong lost his daughter to DIPG over 60 years ago, before he walked on the moon, a stark reminder that while we've made extraordinary advances in many areas of science and medicine, brain cancer remains critically underserved.
"This grant helps bring it into focus. It backs the science, the urgency, and the collective determination to make a difference."
The research project is an example of the University of Newcastle's commitment to helping its communities live better, healthier lives.
* HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.
** Professor Dun is a National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow (2020-2024), a Professor of Medical Biochemistry and Bill and Iris Burges Professorial Chair in the Medical Sciences at the University of Newcastle, Australia, Group Leader of the University's Cancer Signalling Research Group and Deputy Director of the HMRI Precision Medicine Research Program. He is the paediatric brain cancer stream leader of the University of Newcastle's Mark Hughes Foundation Centre for Brain Cancer Research.
