Each child’s cancer is unique at a molecular level. Depending on the molecular makeup of a child’s cancer cells, their cancer may or may not respond to various anti-cancer drugs. This means that two children who have the ‘same’ kind of cancer – for example, acute lymphoblastic leukaemia – may respond very differently to the same treatment.
The Zero Childhood Cancer Program (ZERO) uses the very latest science and technology to offer unique insight into each individual child’s cancer and how it might best be treated. The comprehensive testing and analysis being carried out for each participating child is unprecedented, making ZERO a world leading childhood cancer program and establishing Australia as an international leader in paediatric personalised medicine.
This is an unprecedented opportunity to use 'big data' analysis tools to uncover patterns in the data that were previously hidden."
- A/Prof Mark Cowley, Group Leader, Computational Biology, Children's Cancer Institute
The first step in the journey of a child who joins ZERO is sample collection. As soon as the child is admitted to hospital and enrolled in the national clinical trial, cancer and non-cancer tissue samples are taken and sent for testing and analysis. Any excess sample is frozen and stored in our tumour bank (biobank) for future research.
Testing and analysis
Each child’s cancer sample is subjected to rigorous testing and analysis in our laboratories, as well as partner laboratories in Australia and sometimes overseas, to look for molecular clues (such as specific genetic changes and altered gene activity) that point to possible causes and drivers of the cancer, and any potential treatments that would target these changes. This is followed, where possible, by drug screening and drug sensitivity testing to identify which treatments are likely to be most effective in treating the cancer.
Whole genome sequencing and RNA sequencing
Whole genome sequencing (revealing the precise make-up of each child’s normal or ‘germline’ DNA, as well as their cancer’s DNA) and RNA sequencing are carried out to investigate the presence of precise genetic mutations associated with the child’s unique cancer. This information is analysed using sophisticated, customised bioinformatics, and integrated with other biological and clinical data to provide a complete picture of the genetics of that child’s cancer. This allows us to potentially pinpoint the genetic factors that are driving the growth of the cancer and indicate its likely sensitivity to particular treatments.
In children diagnosed with a brain tumour or sarcoma, DNA methylation profiling is done, providing important information about non-genetic alterations (epigenetics) involved in the child’s cancer. This not only allows more accurate classification of the cancer subtype, but is also relevant to prognosis and predicting response to therapies.
Where possible, advanced robotic technology in our Drug Discovery Facility is used to conduct rapid high-throughput in vitro screening of more than 120 drugs and drug combinations, to identify if a drug or drugs are likely to be effective at killing that child’s cancer cells.
Drug testing in biological models
Where possible, the child’s cancer cells are grown in a treatment surrogate − a mouse ‘avatar’. This allows the most promising candidate drugs to be tested in living models of disease (‘in vivo’ testing) to see how the cancer responds. The best drug candidates are those capable of killing the cancer without damaging normal healthy cells.
Minimal Residual disease testing
In the case of a child with acute lymphoblastic leukaemia, molecular diagnostic testing is done to detect and measure any residual disease − cancer cells that have persisted despite treatment. This guides the introduction of intensified treatment in those children at highest risk of treatment failure.
The results of all these detailed tests and analyses are entered into customised state-of-the-art information management systems. These systems safely store all the laboratory results relating to each child, link them with clinical information, and comprehensive reports are generated for discussion at ZERO’s Multidisciplinary Tumour Board meetings.
Expert panel review and recommendations
Once all the testing and analysis of a child’s tumour and normal samples is complete, a group of specialist doctors and researchers from around the country (the Multidisciplinary Tumour Board) discusses the results and makes recommendations about suitable treatment options. The child’s treating clinician then receives a comprehensive report outlining the findings, including any potentially actionable recommendations, which allows them to develop a personalised treatment plan.
As well as guiding the treatment of each child taking part in ZERO, the comprehensive data collected through testing and analysis provides an invaluable repository of information that can be used to inform existing and develop new, associated research projects.
This means ZERO is not only having an incredible impact on children with cancer today but is also significantly accelerating progress in childhood cancer research that will lead to improved outcomes for children with cancer in the future.