Brain Tumour Research Program

Cancers arising primarily from the brain are the fourth most important type of cancer in terms of life years lost, because these tumours disproportionately affect young people.  They are the most common type of cancer in children.  In addition, one third of all deaths in our society are due to cancer, and in a quarter of those people dying from cancer the tumour will have spread to the brain.

In over 60% of patients with brain tumours, the cancer is incurable, with the average life expectancy being less than one year despite the best available treatments.  It is recognised that the best chance of curing these tumours will be first of all to understand the nature or biology of the tumour, and then develop therapies targeted at the biology.  These are called “biological therapies”.

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Over the past ten years there has been a considerable increase in our understanding of cancer generally, and brain tumours specifically – at both a cellular and a molecular level.  No longer are we limited in our knowledge to what the tumours look like generally, but molecular biology tools and techniques developed during the 1990s have given us an insight into the molecular structure of cancers, including the genetic aberrations and consequent abnormalities of gene expression.

We do believe that over the next ten years it will be possible for us to use our understanding of brain cancers to develop new therapies.  Our laboratories have made considerable progress in developing potential “novel” targets for biological therapies, and we have every expectation that it will be possible to develop effective therapies for brain cancer in the future.  However, further funding is vital to enable the work to continue.  Our laboratories are in a very special position, in that we are able to collaborate closely with many national and international research institutes thereby increasing the rate of the progress of science.

 

  Brain Tumour Research Laboratories

The Brain Tumour Research Program is undertaken in the laboratories of the Department of Surgery at the University of Melbourne, and has close interaction with the Ludwig Institute for Cancer Research, the Walter and Eliza Hall Institute for Medical Research and other university departments. 

The laboratory research primarily investigates the the basic molecular and cellular events that lead to the development of brain cancer.  This includes studying the role of cell-surface receptors in brain cancer growth and invasion and the intracellular signalling pathways that are altered in cancer development.  Particular interest has been in defining the negative regulators of growth signalling pathways and compounds have been identified which can interact and either positively or negatively regulate the aberrant pathways. 

Dr Peter Lock from the Department of Surgery is studying the role f the Tks5-Nck signalling pathway in brain tumour invasion. 

Dr Chris Hovens, in conjunction with his co-workers in a Phase 1 trial have established a compound which inhibits the PI3-AKT pathway, thought to be particularly important in brain tumours and prostate cancer.  A patent has been awarded for this compound, and venture capital raised to commence a clinical trial at The Royal Melbourne Hospital.


 


 Brain Tumour Program - Studies to isolate and characterize the biology of glioma stem cells (Cancer)

There is strong evidence that glioma tumours originate from small populations of malignant “brain tumour stem cells”. Unlike the bulk of the cells within a tumour, brain tumour stem cells have an unlimited potential to multiply and moreover, these cells are highly resistant to chemotherapy and radiotherapy. These cells are therefore thought to represent the primary source of brain tumours and are widely thought to be the most relevant cell type to target when conceiving future therapeutic approaches. On this basis we have begun to isolate brain tumour stem cells from specimens taken from patients receiving treatment at the Royal Melbourne Hospital and are in the process of establishing permanent stocks of the cells for research purposes. The brain tumour stem cells will be implanted into the brains of laboratory mice in order to develop animal models that will closely recapitulate the biology of the original brain tumours. This research will provide a clearer understanding of the brain tumour biology and should enable the development of better, more targeted treatments of this devastating group of diseases.

Brain Tumour Program - Studies relating to epithelial-mesenchymal-endothelial-transition (EMET) and the role of TGF-beta in EGF receptor-driven tumourigenesis, with the aim of gaining a better understanding of tumour vascularisation  (Cancer)

The majority of tumour death occurs due to tumour metastasis. Both tumour growth and tumour spread require angiogenesis, which is thought to be driven by the tumour but originated from host endothelial cells. Could tumour cells behave and function like endothelial cells? This application aims to detect the transition of adult epithelial cells to endothelial cells through a transient mesenchymal state. Our studies should reveal both the molecular and cellular causes of vasculogenic mimicry thus establishing a new paradigm in understanding tumour growth and metastasis. Such novel molecular understanding will open up new anti tumour therapeutic opportunities.

The molecular and cellular mechanisms of the development of epilepsy in patients with brain tumours

In conjunction with the Department of Medicine, researchers from the Department of Neurosurgery are investigating the molecular mechanisms of epilepsy in patients with brain tumours.  Dr Tanya Yuen was awarded the Sir John Lowenthal Research Fellowship from the Royal Australasian College of Surgeons to continue her work which is progressing towards a PhD on the molecular and cellular mechanisms of the development of epilepsy in patients with brain tumours.  In particular, she is looking at the role of glutamate and its receptors and ADAM 22.  This work may have considerable implications beyond epilepsy and brain tumours and help to understand the pathogenesis of epilepsy in those patients without a structural lesion.  Dr Yuen’s supervisors are Professor Andrew Kaye and Associate Professor Terry O’Brien. 

Brain Tumour Program - Studies of the neurobiological mechanism involved in the development of epilepsy in brain tumour patients (Cancer)

Epileptic seizures commonly occur in patients with brain tumours, and are often difficult to control with anti-epilepsy medication. This causes significant morbidity and decreased quality of life for affected patients. The underlying cause(s) of such seizures remains unknown. Moreover this remains a poorly investigated field of research. We hypothesise that there will be identifiable factors involved in the development of these seizures, providing novel insight into their pathogenesis. This process will thus identify novel targets for the development of new medications in the treatment of this disease. This will ultimately better equip clinical practitioners for the care of these patients.
 
 Brain Tumour Program – Photodynamic Therapy

The department continues to study the use of photodynamic therapy to treat brain tumours and the laboratory investigations augment the clinical research program, by identifying new photosensitisers compounds, and enhancing the mechanism of the phototherapy action at a cellular and molecular level.

The department participates in numerous brain tumour clinical research programs at both a national and international level.  This includes participation in the NH & MRC special government initiative on the relationship between mobile telephone usage, electromagnetic radiation and the development of brain tumours.  Numerous studies involved in the use of chemotherapy agents and the treatment of brain tumours have been investigated as part of Phase I, Phase II and Phase III Multicentre Trials.  Members of the department have been instrumental in developing management guidelines for the treatment of brain tumours.