Our neuroblastoma research
How aggressive a neuroblastoma is may depend on which cellular mechanism is 'broken'. Certain cellular mechanisms related to poor prognosis in neuroblastoma have been discovered and explored both at the Garvan and through our many collaborators. Understanding these mechanisms and how they affects treatment efficacy is an important step in increasing the survival rate for aggressive neuroblastoma.
We are also committed to exploring treatments that don't have the harsh, long-term side effects of standard treatments. Standard treatments such as chemotherapy and radiotherapy affect healthy cells as well as cancerous cells, and can lead to undesirable effects such as hearing loss and an increased risk of other cancers. We have been exploring microRNA as a highly specific and effective treatment that will target the genes that cause cancerous cells to grow uncontrollably whilst leaving healthy cells alone.
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Key areas of investigation
miRNA as a new form of targeted treatment
A/Prof Alex Swarbrick and Dr Holly Holliday from the Tumour Progression Lab have been studying the use of microRNA in targeted treatments for neuroblastoma. MicroRNAs are gene regulators - they are able to turn genes on or off and can influence tumour growth. They aim to find out which microRNAs are responsible for slowing down and suppressing tumour growth and the genes they target.
Currently neuroblastoma treatment often involves high doses of chemotherapy which results in life-long side effects such as hearing loss, development problems and an increased risk of developing other cancers. The ultimate goal is to develop a microRNA treatment that can be given in combination with a much lower dose of chemotherapy to reduce the chance of developing serious side effects.
Dr Holliday has so far identified some microRNAs that were successful in killing neuroblastoma cells in a petri dish in combination with low doses of chemotherapy. She is now further testing these microRNAs in mouse models with neuroblastoma to determine how effective the treatment is at slowing and stopping tumour growth within an organism.
Signalling pathways as biomarkers
Dr David Croucher, head of the Network Biology Lab, has looked in to why the prognosis of high-risk neuroblastoma is so poor despite the many forms of treatment being available. He and his many collaborators were able to identify a certain pathway, or mechanism, that was found to be broken in many neuroblastoma patients with poor prognosis. This pathway was identified as the Jun N-terminal kinase (JNK) pathway which is responsible for initiating cell death - a very important process in eliminating cancer cells.
It was found that many standard-of-care neuroblastoma treatments use the JNK pathway to kills the cancer cells. If the JNK pathway is not working, these treatments will not be effective. Alternative drugs that do not need the JNK pathway are now being tested for efficacy by Dr Croucher, in collaboration with A/Prof Swarbrick of the Tumour Progression Lab and Dr Fletcher from Children’s Cancer Institute.
National and international collaborations
- Australian National University, Canberra, Australia
- Children’s Cancer Institute, Sydney, Australia
- Chris O’Brien Lifehouse, Sydney, Australia
- Fudan University, Shanghai, China
- German Cancer Research Center, Heidelberg, Germany
- Ghent University, Ghent, Belgium
- Max Planck Institute for Metabolism Research, Cologne, Germany
- Memorial Sloan Kettering Cancer Center, New York, United States of America
- Monash University, Melbourne, Australia
- Peter MacCallum Cancer Centre, Melbourne, Australia
- Second Affiliated Hospital of Soochow University, Suzhou, China
- St Vincent’s Clinical School, Sydney, Australia
- Sydney Children’s Hospital, Sydney, Australia
- University of Bologna, Bologna, Italy
- University College Dublin, Dublin, Ireland
- University of Cologne, Cologne, Germany
- University Hospital Cologne, Cologne, Germany
- University of Melbourne, Melbourne, Australia
- University of New South Wales, Sydney, Australia
- University of Newcastle, Newcastle, Australia
- University of Sydney, Sydney, Australia
- University of Queensland, Brisbane, Australia
- University of Technology, Sydney, Australia