In 2011, what has become a wonderful partnership between Children’s Cancer Institute and international charity The Cure Starts Now began with a $156,000 research grant. Today, the charity and the DIPG/ DMG Collaborative partners have contributed more than $3 million to the Institute’s research into childhood brain tumours, focusing on the worst of them all, diffuse intrinsic pontine glioma (DIPG).
According to the recipient of that first grant, Professor David Ziegler, DIPG — one of a deadly group of brain cancers called diffuse midline gliomas or DMG — is untreatable and universally fatal, usually within a year of diagnosis.
Working both as a paediatric oncologist at the Kids Cancer Centre in Sydney Children’s Hospital and as head of the Brain Tumour Group at Children’s Cancer Institute, Professor Ziegler said that each time he has to explain to the parents of a child with DIPG that their child is going to die, it hardens his resolve to find a way to treat this deadly cancer.
“Having to deliver such heartbreaking news is extremely difficult, but there is hope for the future. Through dedicated research, and with the help of The Cure Starts Now, I believe we can change the outlook for children diagnosed with DIPG in the future.”
It was also back in 2011 that The Cure Starts Now founded The DIPG/DMG Collaborative, a cooperative effort of independent foundations from around the world helping to fund long term DIPG/DMG research, effectively turning individual philanthropic contributions into a coordinated, high-impact research enabler.
Associate Professor Maria Tsoli, who works as Senior Scientist in the Brain Tumour Group at Children’s Cancer Institute, said this funding has been instrumental to her work at the Institute.
“The support of The Cure Starts Now and The DIPG/DMG Collaborative has been transformative for my research. Their commitment to funding high-impact science has enabled us to pursue important research questions that would otherwise be out of reach, directly driving key discoveries, including identifying new targets and therapies for DIPG, as well as developing preclinical models that are now informing clinical translation.”
“Without their unwavering belief in our work, many of these breakthroughs simply would not have happened.”
Keith Desserich, Chairman and Co-Founder of The Cure Starts Now, said the charity is a leader in non-government funding of paediatric brain cancer research, and is dedicated to pursuing cancer research on those fronts that offer the most promise.
“In the mission to find a cure for one of the world’s toughest cancers, DIPG/DMG, our partnership with Children’s Cancer Institute has been a center nucleus, with 18 research projects spanning more than 15 years,” he said.
Some of the pioneering research projects at the Institute to receive funding from TCSN and the DIPG/DMG Collaborative are described below.
Investigating novel therapies in fatal children’s brain cancers (Dr Jessica Bell): Some brain cancers ooze lactic acid which binds DNA and proteins in cancer cells, making them aggressive and less sensitive to therapies. Using funding from TCSN, I have been able to show for the first-time that DMG cells can be killed by depriving them of lactic acid, using oxamate and supplementing cells with beta-alanine. In our animal models of brain cancer, we have shown that these agents are well tolerated; now we are testing to see if they can increase survival. We are also investigating if other drugs could enhance the killing effect.
A potential new treatment strategy for DMG (Dr Ben Rayner): Most DMGs harbour a histone methylation mutation that effectively promotes tumour growth. We have identified that right next to this mutation is another protein modification called citrullination, which switches off histone methylation. By targeting this, we aimed to switch on the beneficial methylation-dependent pathways, ultimately halting DMG growth. Interestingly, we found that other cellular proteins also become citrullinated and affect DMG growth, and that if we target these in unison, we can kill off the DMG cells. Overall, our research shows that citrullination is an important and previously overlooked factor in how these tumours grow, potentially providing a new treatment strategy for children with DMG.
Dual therapy may hold key to effective childhood brain cancer treatment (A/Prof Maria Tsoli and Prof David Ziegler; published 2026): One of the biggest challenges in targeting DMG is that thousands of genes are activated in the disease, and it has proven extremely difficult to find a way to switch them all off. In this research, we found a way to do that by combining two new-generation drugs known as epigenetic therapies. In our studies, the combination killed DMG cells grown in the lab, and led to tumour death and extended survival in mice. It also appeared to unmask the cancer cells to the immune system, suggesting that adding an immunotherapy could potentially achieve even better results.
New therapeutic approach for children with DIPG (Prof David Ziegler; published 2021): In this research project, we discovered that an anticancer drug developed from the antimalarial drug quinacrine, CBL0137, reverses the effects of the key genetic drivers in DIPG, and has a profound effect in DIPG tumour models. We also found that CBL0137 is even more effective when combined with a second drug, panobinostat, a new type of drug known as a histone deacetylase (HDAC) inhibitor. When used in combination, the two drugs worked synergistically, each enhancing the other’s effects against DIPG.
Discovering New Epigenetic Players in DIPG Oncogenesis (A/Prof Fa Valdes Mora): This project investigated the critical partners, additional epigenetic factors, of the H3.3K27M mutation, the most common genetic alteration driving this disease. By uncovering how these epigenetic factors contribute to tumour development, this research revealed new therapeutic targets. This work addressed a critical unmet need and has the potential to open new avenues for precision treatments for children with DIPG. We then published a review in 2021: Research Update - The H2A.Z-nuclesome code in mammals: emerging functions
Find out more about The Cure Starts Now and the research being supported at https://thecurestartsnow.org.au/
