Brain Cancer

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There are currently no known measures to prevent brain cancer, or screening tests available for early detection of the disease. Patients with the most common and most malignant form of primary brain cancer have a very poor prognosis, with a median overall survival of just 14.6 months, despite invasive surgery, aggressive radiotherapy and chemotherapy.

In collaboration with medical oncologists including Associate Professor Helen Wheeler and Dr Adrian Lee, radiation oncologists, neuro-pathologists and neuro-surgeons, our brain cancer research is aimed at improving treatments and outcomes for brain cancer (also known as glioma or glioblastoma) patients.

Brain cancer is rare, accounting for 1.3% of all cancer diagnoses in NSW

It has the highest ‘average years of life lost’ and highest economic burden of any cancer

Less than 1 in 20 patients with high grade brain cancer survive 5 years

Brain Cancer Research Group Leader: Dr Amanda Hudson

Dr Hudson is a Post-doctoral Research Fellow whose research achievements have been recognised by receiving a Brain Cancer Group Fellowship. Her expertise is in molecular biology, with a major focus of her research being on investigating why brain cancer changes over time and why treatment resistance develops. Her work is contributing to identifying new treatments and treatment strategies for improving the survival and quality of life of those people living with brain cancer.

Projects

1. Teaching an Old Drug New Tricks: Can we repurpose an old drug as a new brain cancer treatment?

Dr Amanda Hudson, A/Prof Helen Wheeler, A/Prof Viive Howell

There is an urgent unmet need for additional therapies to increase patient survival as well as biomarkers to ensure patients with brain cancer receive the right treatment at the right time. We have identified a factor, which can be inhibited using an older generation drug, to improve treatment response in other cancers.

This project will determine whether this factor, measured in a simple blood test is sufficiently sensitive and specific to help doctors determine the best treatment for a patient. We will also determine whether this old drug that inhibits this factor, when given with current therapies, can improve the response of brain cancer to treatment. Through successful completion of this project we hope to “teach an old drug new tricks” and rapidly improve outcomes for brain cancer patients.

Funding: Mark Hughes Foundation (in memory of Olivia Addison) Hunter Medical Research Institute,  The Brain Cancer Group.

2. The immuno-coagulome: an untapped pathway for new therapeutics in glioma

Dr Amanda Hudson, Dr Kelly McKelvey, A/Prof Helen Wheeler, A/Prof Viive Howell

Inflammation and coagulation have functioned together throughout evolution to provide a solid defence against infection, damaged cells and irritants. While these systems work in harmony most of the time, they can also become dysregulated or corrupted by tumours, enhancing tumour proliferation, invasion, dissemination and survival. Unravelling the tumour-promoting interactions that exist between these 2 systems will provide fundamental knowledge for the development of new therapeutic strategies to treat glioma patients.

Funding: The Brain Cancer Group

3. Investigating how glioblastoma tumours change over time to become resistant to treatment

Dr Amanda Hudson, A/Prof Helen Wheeler, A/Prof Viive Howell

While treatment with surgery, radiotherapy and/or chemotherapy may prolong life for patients with glioblastoma, recurrence is inevitable. What is still being discovered is how much these treatments and recurrence of disease affect the molecular profiles of these tumours and how these tumours adapt to withstand these treatment pressures. Understanding such changes will uncover pathways used by the tumour to evade destruction and will elucidate new targets for treatment development. This project examines the differences between matched pre- and post- treatment glioblastoma tumours with the aim to understand changes that occur after treatment and progression of disease.

Funding: The Brain Cancer Group

4. Unravelling the tumour microenvironment to combat brain cancer

Dr Kelly McKelvey, Dr James Wilmott, Dr Connie Diakos, A/Prof Helen Wheeler, A/Prof Viive Howell

Currently, gliomas are treated with multi-modality therapies (surgery, radiotherapy, chemotherapy, targeted-therapy, and experimental immunotherapy), which can interact in both positive and negative ways to control tumour growth. The development and success of robust new therapies for glioma can only occur by considering and understanding the unique microenvironment in which these tumours develop (i.e. the blood brain barrier and CNS immunity), and the potential impact the different therapeutic interventions have, alone or in combination, on both the tumour and surrounding CNS.

This work utilises preclinical models of brain cancer and the only Small Animal Radiation Research Platform (SARRP; Xstrahl, USA) on the east coast of Australia.

Funding: Sydney Neuro-Oncology Group; Sydney Vital Translational Research Centre; Matt Callander Beanie for Brain Cancer (Mark Hughes Foundation) Hunter Medical Research Institute Fellowship.

5. Laying the foundations for improved treatments for IDH-mutated glioma

Angela Cho, Dr Amanda Hudson, Dr Emily Colvin, Dr Sarah Hayes, A/Prof Michael Back, Prof Stephen Ackland (Hunter Medical Research Institute) A/Prof Helen Wheeler and A/Prof Viive Howell

Low grade gliomas are characterised by a relatively indolent clinical course and a good prognosis. However, these gliomas may recur as high grade gliomas, which are more aggressive and are difficult to treat. We will compare matched primary and recurrent brain tumours and identify genes and pathways which have altered, to better understand the potential mechanisms which may drive the change in behaviour of the recurrent tumours. Understanding how these tumours change over time and in response to therapy will lay the foundations for developing better treatments for this rare form of brain cancer.

Funding: Mark Hughes Foundation, Hunter Medical Research Institute, The Brain Cancer Group, University of Sydney and Balnaves Foundation

6. The interaction between coagulation, angiogenesis and inflammatory pathways in glioblastoma

Dr Adrian Lee, A/Prof Helen Wheeler, A/Prof Viive Howell

Patients with high grade brain tumours have a higher incidence of venous thromboembolic (VTE) complications as a result of altered coagulation. Specifically, high grade glioma that carry a particular genetic marker (known as EGFR amplification) are thought to have even higher rates of VTEs which leads to significant morbidity and mortality. This project investigates the interaction between the coagulation system and the genetic marker EGFR to determine whether EGFR is a predictive marker for VTE complications. In addition, the project also investigates whether there are other clinical and biochemical markers in high grade glioma patients that can help predict the likelihood of VTE events, therefore reducing morbidity for glioma patients.

Funding: The Brain Cancer Group, The Rebecca Cooper Foundation

7. MHF Brain Cancer PACT: Mark Hughes Foundation Collaborative Brain Cancer Pre-clinical pipeline for Advancing Cancer Therapeutics

A/Prof Viive Howell, Dr Kelly McKelvey, Dr Amanda Hudson, A/Prof Helen Wheeler

The goal of this project is to accelerate the progress of new therapies for brain cancer from the laboratory to clinical trials. We will accelerate and increase the efficiency of high quality research in brain cancer by providing researchers with easy and collaborative access to brain cancer specific pre-clinical capabilities. This project will exploit existing pre-clinical infrastructure and modelling expertise to establish a collaborative Pre-clinical pipeline for Advancing Cancer Therapeutics (PACT) specific for brain cancer. PACT will include brain cancer models, treatments, design, approvals, testing and collection of required specimens for downstream analysis. This will enable researchers including chemists and physicists who would not otherwise have access to the required facilities, to test agents under development as potential brain cancer therapies. This may involve testing novel agents alone or in combination with standard of care (radiotherapy, chemotherapy) or other therapies to determine their efficacy and possible side-effects.

Funding: Mark Hughes Foundation

8. Development of non-invasive monitoring for brain tumour recurrence and treatment resistance

Angela Cho, Dr Amanda Hudson, Dr Emily Colvin, Dr Sarah Hayes, A/Prof Helen Wheeler and A/Prof Viive Howell

The development of treatment resistance and tumour recurrence is sadly the norm for individuals diagnosed with brain cancer. This project will determine the sensitivity of detecting tumour burden by tumour-specific genetic material in blood samples. Results will be correlated with current monitoring which relies on accurate patient documentation of symptoms followed by Magnetic Resonance Imaging. Sensitive detection of treatment resistance and recurrence will enable earlier cessation of ineffectual treatments, direct selection of 2nd line treatment and improve clinical management. If utility is demonstrated, this work will be expanded to other common brain tumour types.

Funding: Sydney Vital Seed Grant and the Brain Cancer Group

9. A new class of theranostics for malignant brain cancer

Dr Hilary Byrne, Dr Kelly McKelvey, A/Prof Viive Howell, Prof Zdenka Kuncic, Prof Louis Redina

Malignant brain tumours including glioblastoma (GBM) are some of the most intractable and aggressive cancers, with a very poor prognosis and low 5-year survival rate.  This project aims to assess a completely new class of gadolinium theranostics in preclinical models.  Our innovative agents possess a tremendous capacity to target and aggregate within human glioma cell mitochondria in a tumour-selective manner. The expected outcomes of this research will confirm the in vivo potential of this class of theranostics as brain tumour-selective imaging agents for MRI and as radiosensitisers for X-ray irradiation, the first mitochondrial-targeted theranostic platform specifically designed for potential application as dual MRI contrast agents and X-ray radiosensitisers.

Funding: Drug Discovery Initiative Grant

10. Radiosensitisation of high-grade gliomas by modulating glucose metabolism

Dr Han Shen, Dr Kelly McKelvey, Dr Eric Hau

High-grade  gliomas  (HGGs) comprising  glioblastomas  (GBM)  in  adults  and  diffuse  intrinsic  pontine  glioma (DIPG) in children are a devastating group of cancers, representing the leading cause of brain tumour-related death.  Despite advancements  in  multimodality treatment survival  rates  continue  to  be  dismal.  For decades, radiation  therapy  (RT)  has  been  the  cornerstone  of treatment in GBM. This study uses preclinical models of GBM and DIPG to investigate the efficacy of inhibiting glucose metabolism in combination with RT and examine the mechanism of acquired resistance.
Funding: NHMRC

11. New Horizons: Therapeutic applications for medicinal cannabis in the treatment of brain cancer

Dr Matt Dunn, Dr Kelly McKelvey, Dr Adjanie Patabendige, Dr Ameha Woldu, Dr Mengna Chi, Dr Craig Gedye

Brain cancer, in particular high-grade gliomas (HGG), are the leading cause of cancer death in children and adolescents and account for 60-70% of all primary brain and central nervous system cancers in adults. Patients diagnosis with a HGG face a dismal prognosis with an estimated 5-year overall survival rate of 2-3%. In partnership with the Australian Natural Therapeutic Group (ANTG) this project will determine anti-brain cancer efficacy of cannabis in combination with established treatments, namely radiotherapy.

Funding: HMRI Cancer and Medicinal Cannabis Research Project Grant

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