Brain Tumours  

Contact: A/Prof David Ziegler, dziegler@unsw.edu.au

A critical problem in improving treatments for DIPG has been the lack of surgical tissue for biological studies in the laboratory. To address this, we initiated a national DIPG tumour donation program.

With tissue donated from post-mortem samples, we have grown a panel of DIPG neurosphere cultures. These represent a unique platform on which to investigate the biology of DIPG and to test novel therapies. We have also developed unique mouse models of DIPG and performed robotic high throughput screens to identify novel therapeutic approaches. Further combination screens of the most effective compounds have identified potentially useful combination therapies.

Contact: A/Prof David Ziegler, dziegler@unsw.edu.au

We are currently investigating a number of different therapeutic strategies to treat DIPG and other high-risk brain tumours. These strategies include:

• Modulation of cellular metabolism.
  
  
• Targeting the mitochondria – the cancer cell’s powerhouse.
  
  
• Targeting the epigenome.
  
  
• Targeting cellular growth factors and tyrosine kinases.
  
  
• Targeting the cell cycle apparatus.
  
  
• Developing radiation therapy sensitising agents.
  
  
• Investigating novel immunotherapeutic strategies.
  
  

We recognise that none of these strategies alone is likely to be sufficient to eradicate tumours such as DIPG. We therefore have a strong emphasis on developing rational combination therapies.

Contact: A/Prof David Ziegler, dziegler@unsw.edu.au

The Zero Childhood Cancer Program (ZERO) seeks to identify personalised therapies for children with high risk cancers. Within ZERO, the Brain Tumours Group leads the brain tumour arm of the program, which provides genomic analysis, in vitro drug screening, and in vivo personalised xenograft models for children with brain tumours.

In addition to defining novel therapeutic approaches for children participating in the ZERO national clinical trial (which A/Prof Ziegler chairs) in real time, our group leads a research discovery program that utilises the rich database of genomic and drug screening data being generated by ZERO to investigate novel therapies for all high risk childhood brain tumours.

Contact: A/Prof David Ziegler, dziegler@unsw.edu.au

Levi’s project is a dedicated DIPG research project named in honour of 8-year-old Levi Wheeler. The project builds on research previously done at Children’s Cancer Institute. We have already established Australia’s first-ever DIPG tumour bank, which contains samples of tumours from children with DIPG, and have tested a range of drugs against DIPG cells grown from these samples.

To date, we have identified five drugs that appear to be highly effective at killing DIPG cells, and have tested these in our laboratory models of disease. The results have been extremely promising and strongly suggest that a coordinated combination of these drugs has the potential to significantly improve survival in children with DIPG.

We are now conducting a series of experiments to find out the most effective combinations of these drugs against DIPG, and will work with our clinical colleagues to take these drugs to clinical trial in children. By working out which combinations of drugs work best, at what doses, and with which timing, a comprehensive clinical protocol can be developed to use in children diagnosed with DIPG.