Zero Childhood Cancer technologies: step-by-step
Each child’s cancer is unique at a molecular level, determining the responsiveness or resistance of that child’s cancer cells to various anti-cancer drugs. Two children who have the ‘same’ kind of cancer – say acute lymphoblastic leukaemia – and who show the same symptoms, may nevertheless respond very differently to the same anti-cancer drugs. The Zero Childhood Cancer national child cancer personalised medicine program uses the latest innovations and technologies to offer a truly unique insight into an individual child’s cancer to enable identification of the drugs likely to target their cancer most effectively.
Tumour samples taken
When a child is admitted to hospital and enrolled in the Zero Childhood Cancer program, a sample of their cancer is taken. The sample is used for testing and analysis, with any excess sample frozen and stored in our tumour bank (biobank) for future study.
Complex testing and analysis
Each child’s cancer sample is then subjected to rigorous analysis in our laboratories and by partner laboratories in Australia and overseas. The tests that may be undertaken include residual disease testing, targeted gene profiling, whole genome sequencing and whole transcriptome RNA sequencing to look for genetic changes and altered gene activity, and drug sensitivity testing.
Residual disease testingThis molecular diagnostic testing identifies and measures acute lymphoblastic leukaemia cells persisting throughout treatment. It guides the introduction of intensified treatment in those children at highest risk of treatment failure.
Targeted gene profilingThe genetic changes that allow a child’s cancer to thrive, and that indicate its likely resistance or sensitivity to particular anti-cancer drugs are pinpointed as closely as possible. Specific regions of DNA from each child’s tumour and normal tissue, comprising a specially selected panel of hundreds of cancer-related genes, are sequenced to look for mutations.
Whole genome sequencingWhole genome sequencing looks at the entire genome of each child’s normal (‘germline’) DNA and also their cancer’s DNA, to define the genetic changes specifically associated with their individual cancer. Analysing this genetic information using bioinformatics, and integrating it with other biological and clinical data, is a crucial element of the Zero Childhood Cancer personalised medicine program.
Drug screeningState-of-the-art robotic instrumentation allows rapid high-throughput screening of individual patients’ tumour cells against hundreds of approved drugs and drug combinations. This allows scientists to find drugs that specifically kill the individual child’s cancer without damaging the healthy cells.
Drug testing in biological models
Results entered and summarised
Where possible, the individual child’s tumour is grown in a treatment surrogate, a mouse ‘avatar’, to get further indications of which drugs are likely to be most effective for treating that child’s cancer. Avatars are treated with the most promising drugs identified from molecular profiling and laboratory high-throughput drug screening.
The results of the detailed tests and analyses are entered into a customised state-of-the-art Laboratory Information Management System (LIMS) which stores all laboratory results relating to each child, links them with clinical information and generates a comprehensive report. In addition to providing hope and new treatment options to each child with high-risk cancer, the data collected provides a clinical and research repository that can accelerate the search for more effective treatments.
Expert panel review and recommendations
A group of specialist doctors and researchers, the Multidisciplinary Tumour Board, discusses each child’s results and makes recommendations regarding the most suitable treatment options, based on all the laboratory tests that have been undertaken. The child’s clinician then receives a report outlining the findings and uses this personalised information to guide their treatment plans.