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:
2024 Research Funded;
Funding: $50,000
Meningiomas are the most common benign central nervous system (CNS) tumours. Although typically low-grade, these tumours can cause significant morbidity, including functional deficits and seizure disorders. Sex hormone receptors expression in meningioma tissue varies and is not well characterised.
This research project aims to audit the expression of sex hormone receptors in meningioma tumours to expand current knowledge on the relationship between hormone receptor expression, tumour molecular characteristics and patient demographics, presentation of the disease and survival. We aim to better understand meningioma risk factors, disease progression and clinical outcomes. The outcomes of this project will serve as foundation for the development of bioinformatics, artificial intelligence, and preclinical ex vivo models for the identification and functional exploration of new pharmacological targets for adjuvant hormone therapy in meningioma management.
Dr Marguerite Harding
Consultant Neurosurgeon
Flinder Medical Centre
Funded: $50,000
The survival rate for glioblastoma, the most common malignant primary brain tumour in adults, has barely improved, due to limited treatment options. Despite aggressive treatment, and irrespective of initial response to standard therapy, most patients succumb to the disease due to recurrence of the primary tumour through mechanisms of resistance. This proposal aims to identify specific mechanisms by which these complex tumours develop resistance to existing therapies and to develop clinically relevant models to assess approaches to overcome these mechanisms.
Dr Melinda Tea & Dr Briony Gliddon
University of South Australia Centre for Cancer Biology
Funded: $50,000
The South Australian Neurological Tumour Bank (SANTB) is committed to advancing neuro-oncology research in SA. With the increasing numbero f projects that we support, additional FTE is critical to our ability to provide high quality and timely support. New Research Assistant will support the the SANTB which is a vital and expanding resource dedicated to supporting multiple research groups primarily in South Australia as well as interstate and
Overseas. Importantly, the SANTB will be better positioned to provide tailored support for each researcher’s projects, and it will ensure uninterrupted support for specimen collection and reduced delays associated with data collection, which are essential for the research activities and outputs of these groups.
Bree Hodgson
Research Assistant, SANTB
Funded: $50,000
Supporting Adult and Pediatric Phase 1 Study of Autologous GD2-Specific CAR T Cell Therapy in Recurrent GD2-positive Glioblastoma Multiforme: Ongoing Assessment and Dose Escalation Trial.
The Translational Oncology lab is a national leader in the field of CAR-T cell therapy for solid cancers. CAR-T therapy is a novel immune therapy that is manufactured from a patient’s white blood cells.
In the last 12 months we have manufactured 14 clinical CAR-T products, with each product taking 3-4 weeks to make, and the same or greater manufacturing load is expected in the next 12 months. This has led to the appointing of a new research scientist, the Chief Investigator mentioned in this application. Dr Sidra Khan’s role is to contribute to the manufacturing of CAR-T cells and to manage the follow-up of patients infused with CAR-T cells. The grant will be used to extend the current 6-month contract for an additional 6 months, which is essential to ensuring we can continue to effectively manage the growing patient demand for our trials.
Sidra Khan
Research Scientist, Translational Oncology Laboratory / Clinical Trial Unit / Centre for Cancer Biology
2023 Research Funded:
Funding: $100,000 (James & Diana Ramsay Foundation)
Glioblastoma is the deadliest form of brain cancer, yet current treatment options are largely ineffective. In response to this desperate need, we are developing a new treatment for glioblastoma, based on a revolutionary type of ‘living drug’ known as CAR-T cells. In this approach, T cells (part of our immune system) are isolated from a patient’s blood and genetically engineered to give them cancer killing activity. These cells are returned to the patient’s bloodstream; they then travel to the tumour to attack it from within. To achieve our goal of developing successful CAR-T cell therapies for glioblastoma, our team of scientists and doctors first test and optimise potential new therapies in the laboratory. We then move our best performing candidates into clinical trials for Australian patients. We have two brain cancer CAR-T cell trials currently running, but only have funding to treat a limited number of patients. We therefore seek further funding to allow us to treat additional patients, and to support our laboratory-based program to further enhance the effectiveness of these new treatments.
(L) Associate Professor Lisa Ebert B.Sc.(Hons), PhD Senior Research Fellow
Central Adelaide Local Health Network, SA Health -Centre for Cancer Biology
(R) Dr Tessa Gargett, Research Officer
Centre for Cancer Biology, UniSA
Funding: $100,000 (Perpetual)
Glioblastoma (GBM) is the most common and lethal type of brain cancer in both children and adults. Despite advances in detection and treatment the survival rate (less than 5%), has not improved in the past 30 years. Therefore, more effective therapies are desperately needed to extend quality patient survival. Our research team has preliminary evidence that the active compounds of medicinal cannabis, known as phytocannabinoids, are able to kill GBM cells. This project aims to provide the necessary preclinical evidence to support the translation of cannabis therapy to GBM patients by identifying which compounds are the most effective, which patients are most likely to respond to this treatment and how much of the treatment should be prescribed. This innovative and personalised approach, called precision medicine (right drug) and dosing (right amount), using novel cannabis extracts might constitute a revolutionary anti-cancer therapy.
Prof Simon Conn
NHMRC Investigator Leadership Fellow
Flinders Health and Medical Research Institute (FHMRI), Flinders University
Funding: $49,890
Glioblastoma (GBM) has been untreatable, because they invade into other regions of the brain, become resistant to currently available therapies and escape elimination by the immune system. We have identified that GBM cells produce a ‘don’t eat me’ signal known as CD47 to escape from immune cells and which aids migration and invasion. Furthermore, loss of CD47 increases mitochondrial (energy power house of cells) function and metabolism. Therefore, we propose to preclinically evaluate a combination treatment strategy using an antibody that targets CD47 and an inhibitor of mitochondrial metabolism.
Dr Nirmal Robinson M. Pharm, PhD Head, Cellular-Stress and Immune Response Laboratory
University of South Australia - Centre for Cancer Biology
Funding: $50,000
GD2 is a promising tumour marker for CAR T cell immunotherapy for brain tumours, and indeed, we have contributed to the establishment of two clinical trials using GD2-targeting CAR T cell immunotherapies for treatment of adults with glioblastoma and children with diffuse midline glioma. Our pre-clinical findings, however, suggest that enhancing GD2 expression in the tumour is likely to improve clinical responses to this therapeutic approach. Thus, this proposal examines approaches to do this, to improve GD2-targeting CAR T cell immunotherapies for glioblastoma. Successful outcomes could also impact the therapy of children with diffuse midline glioma and forms of medulloblastoma.
Dr Manjun Li, MD PhD
Centre for Cancer Biology, Uni SA
Funding: $50,000
Human induced pluripotent stem (hiPSC) cells have the capacity to mimic the genetic landscape of the human brain across neurodevelopment. Moreover, hiPSC-derived monolayer cultures have demonstrated that key neurodevelopmental features can be recapitulated in-vitro. This has enabled researchers to evaluate neurological disorders across neurogenesis and recapitulate electrophysiological phenotypes. However, whether such lab-grown brain models recapitulate biophysical properties specific to humans is unknown.
Therefore, our project aims to systematically compare the intrinsic firing features of hiPSC- derived neurons with ex vivo cortical human biopsies. If successful, this project will advance the relevance of preclinical models for neurological disorders and ultimately improve bench-to- clinic translation.
Associate Professor Cedric Bardy PhD Director of The Laboratory for Human Neurophysiology & Genetics
Flinders University - College of Medicine and Public Health
Funding: $50,000
The commonest and most lethal aggressive adult primary brain cancer is glioblastoma multiforme (GBM). Standard treatment using surgery, radiotherapy, and chemotherapy is lengthy and modestly extends survival but breeds treatment-resistant disease that almost always causes death. The infiltrative and invasive nature of GBM defeats conventional treatment attempts because removing all disease destroys too much normal brain. Genetically engineering a patient’s own lymphocytes against GBM to make chimeric antigen receptor (CAR)-T cells is a promising new therapy. However, GBM’s hostile micronvironment limits the effectiveness of CAR-T cells. We have discovered two ways that may overcome this limitation of CAR-T cell therapy.
Funding: $11,054 - Brave for Dave
This machine gives us the ability to analyse the immune cells in the blood of mice with brain tumours during our immunotherapy studies. Such information is critical to knowing how to improve immunotherapies. This type of analysis took us 4 hours and requires larger amounts of mouse blood. This machine gives us the same results in less than 5 minutes and from very small amounts of blood.
Dr Briony Gliddon BSc(Hons), PhD Research Fellow
Centre for Cancer Biology, Uni SA
Funding: $50,000
A medical device that performs cllosed system cell selection for cell therapy manufacturing. The system ensures purity of the final cell therapy product so that it can be safely administered to patients and is TGA-compliant.
Dr Tessa Gargett, Research Officer
Centre for Cancer Biology, UniSA
Funding: $50,000
Pete's Army - In Memory of Pete Cutting
Preclinical models that recapitulate key characteristics of glioblastoma, namely invasiveness, heterogeneity, immune microenvironment, and intact blood-brain-barrier are essential for successful clinical translation of research. The immune system is fundamental to how glioblastoma responds to treatments, however, preclinical models that mimic interactions between the immune system and glioblastoma tumour are limited. To overcome this, we propose to develop humanised preclinical model of glioblastoma which will produce human immune cells and which harbor brain tumours derived from patient glioblastoma cells. This will generate superior preclinical models of glioblastoma, leading to improved translation of research and better patient outcomes.
Dr Briony Gliddon BSc(Hons), PhD Research Fellow
University of South Australia Centre for Cancer Biology
Funding: $50,000
Patrick of Coonawarra – In Memory Patrick Tocaciu
Glioblastoma is the deadliest form of brain cancer, yet current treatment options are largely ineffective. In response to this desperate need, we are developing a new treatment for glioblastoma based on a revolutionary type of ‘living drug’ known as CAR-T cells. Here, we aim to maximise the ability of CAR-T cells to enter brain tumours. We will do this by studying blood vessels within brain tumours of glioblastoma patients and preclinical models, to find out what makes them permissive to the entry of CAR-T cells. Then we will engineer our therapy to take full advantage of this gateway, hence enhancing treatment success.
Associate Professor Lisa Ebert B.Sc.(Hons), PhD Senior Research Fellow
Central Adelaide Local Health Network, SA Health -Centre for Cancer Biology
Funding: $46,950
In memory of Rick Schembri
Glioblastoma is the most aggressive form of brain cancer, with a median survival rate of 15 months, which has not changed for decades. Despite surgery, radiotherapy and chemotherapy treatment, tumour recurrence occurs in almost every case of glioblastoma, highlighting a desperate need for new treatment options. Tumour cells have a high demand for energy, often fueled by metabolites supplied by the surrounding healthy brain cells. This project aims to identify new therapeutic targets in aggressive glioblastoma tumours by inhibiting supportive metabolic networks in the microenvironment to improve brain cancer patients’ survival.
Dr Chloe Shard, PhD Postdoctoral Researcher
University of South Australia Centre for Cancer Biology
2022 Research Funded:
Funding: $50,000
Glioblastoma is the deadliest form of brain cancer, with limited treatment options. We are developing a new treatment for glioblastoma, based on a revolutionary type of ‘living drug’ known as CAR-T cells. In this approach, T cells are isolated from a patient’s blood and genetically engineered to give them cancer-killing activity. These cells are returned to the patient’s bloodstream; they then travel to the tumour to attack it from within. We recently received regulatory approval to test this therapy in brain cancer patients. Here, we seek funding to support the treatment of the first 6 glioblastoma patients in this clinical trial.
Associate Professor Lisa Ebert B.Sc.(Hons), PhD Senior Research Fellow
Central Adelaide Local Health Network, SA Health -Centre for Cancer Biology
Funding: $49,991
More effective therapies are desperately needed for glioblastoma. Accumulating evidence suggests that sphingosine-1-phosphate, a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays a crucial role in the progression of glioblastomas. Whilst both SphK1 and SphK2 have been implicated in glioblastoma, the distinct function of each kinase in both the tumour and tumour microenvironment remains unclear. In this proposal, we will examine brain tumour growth in SphK1 and SphK2 deficient mouse models to investigate the specific roles each of the sphingosine kinases play in glioblastoma pathogenesis. Successful outcomes will provide new therapeutic targets for glioblastoma.
Dr Briony Gliddon BSc(Hons), PhD Research Fellow
University of South Australia Centre for Cancer Biology
Funding: $49,780
Glioblastoma (GBM) is an aggressive type of brain cancer with a very low median survival (11-15 months). GBM cells adapt to grow in a low oxygen (hypoxia) environment and overexpress ‘don’t eat me’ signal CD47 to evade from immune cells. These mechanisms render GBM cells resistant to therapies. Hypoxia perturbs metabolism and protein synthesis which is destructive to normal cells. However, GBM cells overcome metabolic and ER-stress to survive and grow. We hypothesise that the ‘don’t eat me’ signal CD47 helps GBM cells to adapt and regulates cellular mechanisms that help GBMs to proliferate and migrate. Therefore, we propose to understand the CD47 driven mechanisms that facilitate the growth of GBMs and pharmacologically target CD47 as a therapeutic intervention to treat GBM.
Dr Nirmal Robinson M. Pharm, PhD Head, Cellular-Stress and Immune Response Laboratory
University of South Australia - Centre for Cancer Biology
Funding: $31,000
Glioblastoma Multiforme is an aggressive brain cancer with poor prognosis and survival. Tumours recur after treatment as cells develop resistance to chemotherapy, proliferate and aggressively invade resected and healthy brain tissues. Current research focuses on increasing sensitivity to chemotherapeutic drugs but not on limiting invasive capabilities of these cells. No pharmacological agents that target cell motility mechanisms are used currently as tools for limiting GBM invasiveness during eradication treatments. This project focuses on characterizing pharmacological compounds identified from a comprehensive screen of natural compounds sourced from Davis Open Access Compound library that effectively inhibit invasion of glioblastoma cells.
Dr Sunita Ramesh, Biological Sciences, Lecturer
Flinders University
Funding: $49,992
Brain tumours are difficult to treat, have a high fatality rate, and a devastating impact on the quality of life of patients. Thus, new therapies for brain tumours are desperately needed. In the last few years, immunotherapies have offered great hope for brain tumour treatment. Unfortunately, this hope has not yet translated into better outcomes for patients due largely to brain tumour-induced systemic immunosuppression. This proposal aims to overcome this problem in order to improve the potency of brain tumour immunotherapies. Successful outcomes in this work have the potential to dramatically improve the survival outcomes for brain tumour patients
Dr Melinda Tea BLabMed(Hons), PhD Research Fellow
University of South Australia Centre for Cancer Biology
Funding: $50,000
The effectiveness of brain cancer drugs is best assessed by measured cancer cell growth using in vitro colony-forming assays. These are currently quantified manually, which is subjective and time-consuming. The GelCount is an automated counting and analysis platform which would significantly reduce the time required to screen new drugs.
Dr Melinda Tea BLabMed(Hons), PhD Research Fellow
University of South Australia Centre for Cancer Biology
2021 Research Funded:
Funding: $43,000
Project: In the most devastating form of brain cancer – glioblastoma – the same few regions of our DNA are commonly mutated. However, despite the low number of these commonly occurring mutations, we know very little about how this actually causes cancer, or how it can help us treat brain cancer more effectively.
By replicating these common genetic mutations in normal brain cells, we have, for the first time, created unique models of brain cancer that represent each major subtype of known glioblastomas. We will characterise these at the finest possible resolution, down to single cells, to understand how brain cancers arise and how we might better intervene to treat them.
Dr Brett Stringer MBBS PhD Brain Cancer Research Fellow
Flinders University - Flinders Health and Medical Research Institute
Funding: $32,743
Project: The SA Neurological Tumour Bank(SANTB) obtains brain tumour tissue from the Flinders Medical Centre operating theatres and blood samples which are processed prior to freezing or passing on to research groups.
The SANTB laboratory currently lacks two important pieces of equipment required for processing specimens and relies on using shared and aging equipment in other laboratories. Potentially infectious, these specimens pose a risk to the laboratory staff required to process them and minimising processing time is critical to preserve the integrity of the tissue. Access to this equipment within our laboratory will remove the need to transport potentially infectious specimens between laboratories and streamline our workflow facilitating the rapid and sterile processing of specimens.
Dr Santosh Poonnoose
FRACS Director of South Australian Neurological Tumour Bank
Flinders University - Department of Neurosurgery
Funding: $42,248
Project: Cancer survival rates are the highest they have ever been (69% of all cancers), reflecting advances in early diagnoses and effective treatments (AIHW 2020). While this is a terrific achievement, a new challenge has emerged.
One in three cancer survivors describes long-term side effects undermining their overall quality of life (Macmillan Cancer Support 2013). A significant debilitating side-effect reported is chemotherapy-induced cognitive impairment. Patients often experience diminished capacity in memory, processing speeds, attention, executive function, and reduced mental health (Boscher et al. 2020).
Therefore, our project aims to investigate the underlying neurotoxic side-effects of chemotherapies pre-clinically with innovative human brain tissue models.
Associate Professor Cedric Bardy PhD Director of The Laboratory for Human Neurophysiology & Genetics
Flinders University - College of Medicine and Public Health
Funding: $42,809
Project: Glioblastoma (GBM) is an aggressive type of brain cancer with a very low median survival (11-15 months). GBM cells adapt to grow in a low oxygen (hypoxia) environment and overexpress ‘don’t eat me’ signals to evade from immune cells.
These mechanisms render GBM cells resistant to therapies. Hypoxia perturbs protein synthesis and damages Endoplasmic Reticulum (ER-stress) which is destructive to cells. GBM cells overcome ER-stress by degrading damaged ER through a process termed as ER-phagy. We propose that inhibiting ER-phagy not only kills GBM cells, it also reduces the expression of ‘don’t eat me’ signals which further promotes GBM clearance.
Dr Nirmal Robinson M. Pharm, PhD Head, Cellular-Stress and Immune Response Laboratory
University of South Australia - Centre for Cancer Biology
Funding: $43,000
Project: Glioblastomas are aggressive brain tumours with extremely poor patient outcomes. Currently treatment consists of surgical removal, and post-operative radio/chemotherapy. Despite aggressive therapy, the disease invariably progresses or recurs as resistance to chemotherapy drugs develops. Thus, more effective therapies for this cancer are desperately needed.
Immunotherapy, using the patient’s own white blood cells engineered to kill cancer has shown striking outcomes in a number of cancers, but continues to be challenging for glioblastoma therapy. In this project we aim to better engineer these white blood cells so that they can traffic more effectively to the brain where they can kill glioblastoma.
Dr Briony Gliddon BSc(Hons), PhD Research Fellow
University of South Australia Centre for Cancer Biology
Funding: $38,500
Project: This project will explore the diagnostic utility of a novel magnetic resonance imaging technique known as magnetic resonance fingerprinting.
The project will develop methods such as graphical analysis and visualization tools, as well as artificial intelligence (AI) technology for analysing brain imaging performed in patients with brain cancers undergoing neurosurgery.
The methods will be developed to assist with certain diagnostic dilemmas often encountered by radiologists and neurosurgeons. By resolving these dilemmas pre-operatively, neurosurgeons will be able to better select patients for surgery and improve surgical planning, thereby reducing the risks and promoting the overall safety of neurosurgery.
Dr Minh-Son To BPharm (Hons), BMath&CompSci (Hons), MBiostat, MD, PhD Casual Professional Research
Flinders University - College of Medicine and Public Health
Funding: $43,000
Project: Glioblastoma is the deadliest form of brain cancer, with no effective treatments. We are developing a new treatment for glioblastoma, based on a revolutionary type of ‘living drug’ known as CAR-T cells. In this approach, T cells are isolated from a patient’s blood and genetically engineered to give them cancer-killing activity.
These cells are returned to the patient’s bloodstream; they then travel to the tumour to attack it from within. This project will analyse patient tumours to discover molecular pathways that control T cell entry from the bloodstream. This information can then be used to optimise our CAR-T cell therapy.
Dr Lisa Ebert B.Sc.(Hons), PhD Senior Research Fellow
Central Adelaide Local Health Network, SA Health -Centre for Cancer Biology
Funding: $43,000
Project: Glioblastoma is a heartbreaking diagnosis and most of glioblastoma patients are uncertain of the potential benefit they could receive from different available treatment options.
In this project, we will measure, for the first time and patient-by-patient, the survival benefit in glioblastoma patients of different treatment options, including also those currently in clinical trials.
This result would have profound implications in the clinical management of glioblastoma by an enhanced capacity to:
This will constitute a significant advance to improve survival and quality of life for glioblastoma patients.
Dr Guillermo A. Gomez PhD, Senior Research Fellow, Laboratory Head
University of South Australia - Centre for Cancer Biology
Funding: $37,270
Project: The South Australian Neurological Tumour Bank (SANTB) currently collects and banks brain and spinal cord tumour tissue samples and clinical information from consenting patients undergoing neurosurgery. These specimens are available to researchers in SA and interstate to facilitate research projects into neurological cancer.
The aim of this project is to greatly expand the existing capabilities of the SANTB by developing the capacity to collect each participant’s imaging data (MRI, CT scans etc) and incorporate the SANTB into PHenotyping Outcomes for clinical Care, Quality, and Service (PHOCQUS), a comprehensive clinical data linkage initiative led by Flinders University.
Dr Rebecca Ormsby BSc (Hons), PhD Coordinator, SA Neurological Tumour Bank, Research Associate
Flinders University - College of Medicine & Public Health
Value: $25,000
Brain tumours kill more people under 40 than any other cancer. The survival rate for glioblastoma, the most common malignant primary brain tumour in adults, has barely improved due to limited treatment options. Over time, the disease returns and patients quickly succumb.
Current preclinical models of glioblastoma are mostly limited to studies of the original tumour. These models fail to take into account the tumours that recur following short-term success of initial treatment with surgical resection followed by chemoradiotherapy.
We aim to develop advanced preclinical models of recurrent glioblastoma which in future can be used to assess new therapeutic options.
Dr Melinda Tea BLabMed(Hons), PhD Research Fellow
University of South Australia Centre for Cancer Biology
Funding: $25,000
Project: There is a critical need for better imaging of high grade glioma towards enabling the delivery of more accurately targeted treatment including radiation therapy, a key requirement to prolonging survival without impacting on patients quality of life.
Our research team is developing a magnetic resonance imaging agent that specifically targets cells of the tumour microenvironments, with the aim of providing improved delineation of brain tumours on MRI. This approach has the potential to enable mapping the most aggressive tumor areas which could then receive “boost” radiation doses, including with cutting edge proton therapy and MRI-Linac technologies.
Prof Benjamin Thierry Bio-eng, PhD Research Professor, Bioengineering UniSA
Funding: $30,000
Project: 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.
Dr Lisa Ebert
University of South Australia, Centre for Cancer Biology
Funding: $29,972
Project: 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.
Dr Briony Gliddon
University of South Australia, Centre for Cancer Biology
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.
Dr Nirmal Robinson
University of South Australia, Centre for Cancer Biology
Funding: $29,856
Project: 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.
Dr Guillermo Gomez
University of South Australia, Centre for Cancer Biology
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.
Dr Alexandra Whittaker
Paediatric Brain Tumour Research, University of Adelaide
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.
Dr Melinda Tea
Centre for Cancer Biology, University of South Australia
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.
Dr Lisa Ebert
Centre for Cancer Biology, University of South Australia
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.
Dr Briony Gliddon
Centre for Cancer Biology, University of South Australia
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.
Dr Guillermo A. Gomez
Centre for Cancer Biology, University of South Australia
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.
Dr Quenten Schwartz, PhD
University of South Australia
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.
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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