Brain Cancer

NEW-Brain2

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

The goal of our research is to identify novel prognostic biomarkers and therapeutic targets for brain tumour patients to improve patient outcomes.

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, known as Glioblastoma Multiforme (GBM), have a very poor prognosis, with a median overall survival of just 14.6 months, despite invasive surgery, aggressive radiotherapy and chemotherapy.

The overarching goal of this study is to identify through pre-clinical testing, strategies that can enhance efficacy of current standard of care chemotherapy for patients with glioblastoma. Glioblastoma has the highest burden of disease of any cancer in terms of average years of life lost per patient, estimated internationally to be over 20 years. Treatment strategies which are able to slow disease progression can also reduce the neurological symptoms associated with the disease which will ultimately lessen the burden on the families of glioblastoma patients.

  1. 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 Sydney Neuro-Oncology Group

2. 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, Sydney Neuro-Oncology Group and University of Sydney and Balnaves Foundation

3. Unravelling the Tumour Microenvironment to Combat Brain Cancer

 Dr Kelly McKelvey, Dr Connie Diakos, A/Prof Viive Howell

 Brain cancers (gliomas) are among the most debilitating and lethal of human cancers, with limited treatment options available. 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.

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

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

Brain cancer is a devastating and life changing disease. First line treatment has not changed for over a decade and the number of patients surviving five years beyond their diagnosis remains unacceptably low. Patients who develop treatment-resistant disease and progress on the current standard of care therapies sadly have no further options. 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 from brain cancer patients.

Funding: Mark Hughes Foundation

5. 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, 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