Dr. Hamza Anwer, Head of Research at Cure Brain Cancer Foundation shares his highlights from the 2025 Australian Children’s Brain Cancer Conference (ACBCC) in Brisbane, Queensland.
“From 19 to 21 March, I had the pleasure of representing CBCF as a Foundation Partner at the ACBCC in Brisbane, Queensland. The event was a chance for researchers to come together in the one room to share insights and build synergy towards a common goal: giving children a fighting chance against brain cancer and eradicating this insidious disease. The event brought together researchers from across Australia and beyond, with speakers hailing from the USA, UK, and Asia.
I was incredibly fortunate to attend and hear from renowned experts as they presented their groundbreaking work and engaged in thought-provoking discussions. These conversations went beyond sharing findings—they fostered an open platform for collaboration, where researchers exchanged ideas, challenged perspectives, and explored new directions in the fight against paediatric brain cancer. This collective effort not only advanced scientific understanding but also strengthened the global network of paediatric brain cancer researchers dedicated to making a difference.
I wanted to take the opportunity to highlight just some of the many key presentations from the conference, showcasing the groundbreaking research and innovative approaches being developed to tackle paediatric brain cancer. My goal is to share the incredible work being done by experts worldwide, shining a light on new discoveries, emerging treatment strategies, and the collaborative efforts driving progress in this critical field.
Brain Tumours: From Origins to Relapse Prevention (Prof. Richard Gilbertson)
In this talk, Prof. Gilbertson offered a fascinating and detailed look into his groundbreaking research on paediatric brain tumours. Moving beyond the simplistic view of treating all brain tumours the same, his work focuses on understanding their developmental origins, identifying novel therapeutic targets, and ultimately, preventing relapse.
Fascinatingly, his research team, through extensive gene expression profiling, uncovered the developmental roots of several paediatric brain tumour subtypes. A significant breakthrough involved the tumour suppressor gene FOX03. Contrary to initial expectations, their research demonstrated that the loss of FOX03 alone is sufficient to cause medulloblastoma in mice. This is a landmark finding, making FOX03 only the second tumour suppressor gene (after PTCH) shown to have this effect, and providing a crucial new therapeutic target.
Prof. Gilbertson then shifted focus to the immune system’s role in brain tumour development and progression and discussed the work of Dr. Elizabeth Cooper. Elizabeth Cooper’s research challenged the long-held belief that the brain’s immune system is passive. She demonstrated that the embryonic brain’s immune system differs significantly from the postnatal system, and that brain tumours exploit this difference to create an immunosuppressive environment. Her work revealed the crucial role of hematopoietic stem cells in the skull, which sample the brain via CSF and migrate into tumours, contributing to immune suppression. This finding suggests a potential immunotherapy approach by targeting the communication between the tumour and these stem cells, potentially restoring immune recognition and eliminating the tumour. Her experiments showed that a single antibody dose targeting this communication pathway effectively eliminated tumours in mice.
Finally, Prof. Gilbertson then introduced the work of Amir Jassim. Amir’s research tackles the limitations of current cancer models, which oversimplify how cancers evolve and respond to treatment. He uses a novel approach: treating gene expression data like a text corpus. This allows his machine learning system, REsistance through COntext DRift (RECODR), to analyse not just which genes are active, but how they interact with each other, revealing dynamic shifts in the tumour’s transcriptome – even when gene expression levels remain constant. This approach identifies genes driving relapse and suggests potential drug targets, moving beyond simplistic analyses and opening doors to more effective, personalized therapies.
Development of the Diffuse Midline Glioma ADvanced mAchine-learning Precision Treatment Strategy (DMG-ADAPTS)
In this talk, Prof. Matthew Dun highlights the unique characteristics of diffuse midline glioma (DMG) and strategies used to tackle it head on.
Diffuse midline gliomas (DMGs) exist in a “cold” microenvironment, lacking effective T-cells but rich in diverse myeloid cells. This characteristic, along with the tumour’s high heterogeneity (multiple subclones with varying mutations), complicates treatment. Effective treatment requires a multifaceted approach combining existing therapies strategically. This includes optimizing CAR T-cell therapies, exploring precision therapies targeting vulnerabilities like CLPP (using ONC201), and utilizing immunomodulatory agents such as the adenovirus DNX2401, possibly in combination with ONC201. Methionine metabolism is another potential therapeutic target.
Prof. Dunn then highlighted his work with The DMG ADvanced machine learning-Assisted Precision Treatment Strategy (ADAPTS) Platform. ADAPTS is an analysis pipeline integrating multiomics data from patient biopsies, cerebrospinal fluid (CSF), blood samples, patient-derived xenograft (PDX) tissues, and immune cell modelling. DMG-ADAPTS is a platform aiming to personalize DMG treatment. It involves pre-treatment biopsies, 24-hour drug exposure, and multi-omic sequencing to predict individual tumour responses to a panel of therapies. This data will be used to create a deep learning model, guiding sequential therapy choices for patients and validated in preclinical models.
Advancing Brain Tumour Care Through International Collaboration: Insights from PNOC
The Paediatric and Young Adult Brain Tumour Consortium (PNOC) is revolutionizing paediatric brain tumour treatment. This innovative international group is focused on precision medicine, rapidly translating research into accessible global therapies. They’re tackling significant challenges like standardizing trials across diverse settings and improving response assessment using AI-powered tools and volumetric MRI analysis. PNOC is running multiple trials, including precision medicine approaches (PNOC08), real-time drug screening with a move towards 3D organoids, a combination therapy platform trial (PNOC022) now amended to include an oncolytic virus arm, and immunotherapy efforts using synNotch-CAR T cells. The ultimate goal? Faster, more effective treatments accessible to all children, regardless of location or socioeconomic background.
Single-cell Analysis of ONC201 and Paxalisib Resistance Mechanisms in Diffuse Intrinsic Pontine Giloma
This talk highlighted a recent study investigated resistance mechanisms to ONC201 and Paxalisib, two drugs currently in a clinical trial for DIPG (diffuse intrinsic pontine glioma), an aggressive paediatric brain tumour. While the combination initially showed promise, patients experienced toxic side effects. Using immunocompetent mouse models, researchers found that ONC201 monotherapy failed to improve outcomes, but the ONC201/Paxalisib combination did offer survival benefits. Single-cell RNA sequencing revealed that treatment pushed DIPG cells towards a mesenchymal-like state, a potential resistance mechanism. This shift was associated with MAP kinase pathway activation, surprisingly, despite ONC201’s known mechanism involving its downregulation. The study presented suggests that the immune microenvironment plays a crucial role, with ONC201 impacting myeloid cells, leading to immunosuppression via molecules like PD-L1 and NOX2. In conclusion, the presenter highlighted that future strategies should consider multi-faceted approaches targeting immunosuppressive features and the MAP kinase pathway.”
Main image: Professor Richard Gilbertson presenting at the Australian Children’s Brain Cancer Conference. Originally posted by Cure Starts Now Australia via Instagram.
