Brain cancer (including brain tumours) kills more children than any other disease, and more adults under 40 than any other cancer. In Australia, it claims around one life every seven hours.

This is because brain tumours can spread and invade the brain, causing devastating consequences such as brain swelling.

With your support, we can fund research to:

  • Decrease brain swelling to improve quality of life
  • Reduce invasiveness to enhance surgical brain tumour treatments
  • Impede brain tumour growth to prolong survival

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Optimising a new immunotherapy approach for glioblastoma

Dr Lisa Ebert is a Senior Research Fellow at the Centre for Cancer Biology in Adelaide. Her research focuses on cancer immunotherapy: a new type of cancer treatment that uses a patient’s own immune system to fight their cancer. Such approaches are yielding exciting new therapies for some cancer types. Sadly, however, these discoveries are yet to benefit patients with primary brain tumours such as glioblastoma – a devastating disease with no effective treatment that claims the lives of around 1,000 Australians every year.

With the ongoing support of the NRF, Dr Ebert and her team are working to change this outlook, by developing a new treatment for glioblastoma using CAR-T cells. This cutting-edge approach involves ‘super-charging’ a patient’s own immune cells to enable them to specifically destroy cancer cells. With encouraging pre-clinical results, this research is set to enter clinical trials in glioblastoma patients within the next 12-18 months.

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Dr Lisa Ebert

University of South Australia, Centre for Cancer Biology

Targeting Cyclin-dependent kinase 4 in glioblastoma

Glioblastoma is the most commonly diagnosed brain tumour in adults; it is a very aggressive and highly fatal cancer with a median survival of less than 15 months. The poor survival of patients affected by glioblastoma has remained virtually unchanged for the last 30 years. Currently treatment consists of surgical removal, post-operative radiation therapy and chemotherapy. Despite this aggressive therapy, the disease invariably progresses or recurs as resistance to chemotherapy drugs develops. For these reasons, the development of new drug targets and effective targeted therapies for this cancer are essential. Our recently funded NRF grant project aims to use an established clinically relevant mouse model of glioblastoma to test the efficacy of some newly developed drugs which have shown to be highly effective at killing glioblastoma cells by stopping them from dividing.

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Dr Briony Gliddon

University of South Australia, Centre for Cancer Biology

Targeting Endoplasmic Reticulum-specific autophagy using a small molecule to treat glioblastoma

Glioblastoma multiforme (GBM) is an aggressive type of brain cancer with a median survival of 11-15 months. Very little is achieved in extending the life expectancies of patients with the currently available therapies.

The environment in which GBM grows is low in oxygen (hypoxia) which is lethal to normal cells, but cancer cells have evolved mechanisms to adapt and grow. Importantly, these mechanisms also render GBM cells resistant to therapies.

Endoplasmic Reticulum (ER) are structures within cells where proteins are produced and has a central role in maintaining cellular homeostasis. Hypoxia in the tumour perturbs protein synthesis and ER (ER-stress) which is destructive to normal cells.

We have discovered that GBM cells overcome ER-stress by degrading stressed parts of ER through a process termed as ER-phagy. We propose that inhibiting ER-phagy using a drug in combination with currently available therapies could be an efficient alternative therapeutic strategy to treat GBM.

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Dr Nirmal Robinson

University of South Australia, Centre for Cancer Biology

Identification and targeting of the master regulators of glioma cancer cell plasticity to overcome therapy resistance in glioblastoma

Significant progress has been made in characterizing genetically and functionally diverse GBM subtypes as well as identifying the key oncogenic signals that drive their progression. However, this knowledge has not advanced clinical management of the disease. Indeed, the list of therapeutic agents in phase III and phase IV clinical trials for GBM reveals that only a few of the known GBM activated signalling pathways are currently being targeted in the clinical space. Lack of pipelines to translate fundamental knowledge into clinical trials, highlights the lack of systematic efforts to target intrinsically heterogeneous GBM tumours.

My laboratory combines expertise in patient derived glioblastoma tumour organoid models, bioprinting and bioengineering approaches with single-cell RNAseq, genome-editing, multiphoton microscopy and artificial intelligence, to develop physiologically relevant patient-derived pre-clinical assays that can be used for pre-clinical test of new therapies against glioblastoma as well as identify the molecular drivers of glioma stem cell plasticity and how they cooperate with the tumour microenvironment to develop resistance.

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Dr Guillermo Gomez

University of South Australia, Centre for Cancer Biology

Inflaming the Brain: Chemotherapy effects on Cognitive Function in Child Cancer Survivors

For children who survive childhood cancer, the burden continues, with up to 70% of survivors experiencing chemotherapy-induced cognitive impairment (CICI). CICI impairs attention, and memory, which profoundly impacts academic and social performance, as well as quality of life. To date, the brain changes that give rise to these impairments are unknown. In this study we will determine whether a specific type of inflammation in the brain contributes to CICI development over an acute and chronic time course. The results will facilitate development of targeted therapies for prevention of CICI, in addition to informing clinical assessment protocols and survivorship care plans.

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Dr Alexandra Whittaker

Paediatric Brain Tumour Research, University of Adelaide

Developing a comprehensive glioblastoma brain tumour resource for testing new and existing brain tumour therapies

Glioblastoma (GBM) is the most commonly diagnosed malignant brain tumour in adults, affecting approximately 1000 Australian adults annually. With very few treatment options available, it is a highly fatal cancer with a median survival of less than 15 months and less than 5% survival after 5 years. Our goal is to generate a well characterised bank of GBM brain cancer cells, derived from patient tumour tissue, growing in the laboratory and in animals. These cells will provide a powerful resource for GBM research, both locally and nationally, which may lead to improved therapies for these devastating brain tumours.

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Dr Melinda Tea

Centre for Cancer Biology, University of South Australia

Arming a patient’s immune system to treat aggressive brain cancer

Glioblastoma (GBM) is a highly aggressive form of brain cancer. Most patients only survive for around 15 months after diagnosis, and there have been no significant improvements to treatment for more than 10 years. Here, we aim to develop a new and highly targeted treatment for GBM using Chimeric Antigen Receptor (CAR)-T cells. This type of therapy uses a patient’s own immune system to attack their cancer cells and has shown remarkable success in treating some types of leukaemia. Our new data suggests that we may now be able to adapt this approach to treat GBM.

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Dr Lisa Ebert

Centre for Cancer Biology, University of South Australia

A new approach to deliver drugs to brain tumours

The blood-brain barrier is a major impediment to the treatment of brain tumours. Many drugs that may otherwise have potent anti-brain tumour properties, cannot cross the blood-brain barrier, and thus are ineffectual as brain tumour therapeutics. This proposal builds on recent findings that FTY720, an approved drug for the treatment of multiple sclerosis, can cause short term opening of the blood-brain barrier. Thus, we propose to examine the potential re-purposing of FTY720 to allow the entry of existing anti-cancer drugs across the blood-brain barrier and into brain tumours. Successful outcomes will, therefore, provide new therapeutic strategies to treat brain tumours.

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Dr Briony Gliddon

Centre for Cancer Biology, University of South Australia

Region-specific brain organoids for rapid and personalised pre-clinical test of treatments for glioblastoma

Glioblastoma (GBM) prognosis and treatment is profoundly affected by its anatomic location. Given the importance of tumour location and the microenvironment in GBM progression, there is an urgent need for the development of in-vitro models that facilitate the analysis of brain tumours in a more physiologically and relevant 3D setting. For this we will develop engineered synthetic hydrogel platforms to grow region specific human brain organoids to precisely model GBM progression in patient’s brain anatomical microenvironment. This will permit us to screen for drugs that stop tumour growth and invasion and identify the genes and pathways that drive these processes.

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Dr Guillermo A. Gomez

Centre for Cancer Biology, University of South Australia

Investigating the role of 14-3-3ζ in medulloblastoma, childhood brain cancer

Medulloblastoma arises from abnormal growth of cerebellar granule cells and is the leading cause of cancer-associated death in children. There is a desperate need to understand the molecular defects underlying this malignancy so that new therapies can be devised. Our unpublished work demonstrates that the scaffolding protein 14-3-3 is a key regulator of the sonic hedgehog signalling pathway which is thought to drive the growth of cerebellar granule cells, and medulloblastoma. We now plan to test if removal of 14-3-3 will reduce the burden of medulloblastoma in cell models of this disease.

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Dr Quenten Schwartz, PhD

University of South Australia

The establishment of a comprehensive database management system for the South Australian Neurological Tumour Bank

The SA Neurological Tumour Bank (SANTB) is a not-for-profit resource established to collect and bank blood and neurological tumour tissue from patients undergoing surgery to diagnose or remove their tumour. These specimens are available to researchers in SA and interstate to facilitate research projects into neurological cancer. NRF funds will help to establish and maintain a secure, customizable, web-based database management system to capture and link accurate, reliable and standardized patient clinical data (eg. pathology, treatment, survival) to each specimen. Obtaining comprehensive clinical data is extremely important to maximize the research value of each tumour collected in the drive to improve the outcome of patients with neurological cancer.

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Dr Rebecca Ormsby BSc (Hons)

PhD Coordinator, SA Neurological Tumour Bank

Coordinator, SA Brain Bank at the Centre for Neuroscience (Human Physiology)

Flinders University

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