Every year close to 1,000 children and young people in Australia are diagnosed with cancer, and tragically, three children die from cancer every week. A major challenge is that every child and every cancer is unique – meaning the current one-size-fits-all standard treatment options do not always work.
One of the world’s most comprehensive personalised medicine programs for children and young people with cancer, ZERO aims to identify the precise make-up of each individual child’s cancer by using sophisticated genomic tests (whole genome sequencing, whole transcriptome sequencing and methylation profiling) to identify the molecular changes (including “mutations”) driving their cancer, and matching these with treatments most likely to target their unique cancer. The aim is to identify a personalised treatment plan for each child.
The team of researchers and clinicians studied the genomic data from the first 250 children enrolled and identified the molecular, or genetic, basis of a child’s cancer in more than 90 per cent of cases. As a result, 70 per cent of the children had at least one new treatment option identified based on their cancer’s genetic makeup within nine weeks.
According to Associate Professor David Ziegler, clinician researcher and Co-Chair of ZERO’s national clinical trial, “these are very optimistic early results for children with the highest risk cancers,” he said. “We have shown that ZERO has the potential to find personalised, novel treatment strategies for children with the most aggressive cancers who in many cases had no other treatment options available. Patients who received the molecularly informed, recommended therapy had a much higher rate of clinical benefit than we would expect from non-targeted approaches.”
The early results of those children who received the recommended therapy show that in 30 per cent of cases the tumour shrank, and in some patients completely regressed. In another 40 per cent of cases the tumour stopped growing and stabilised.
Associate Professor Ekert, Translational Tumour Biology, Group Leader, Children’s Cancer Institute explains, “the fact that in more than 90% of cases the genetic cause of the cancer was identified is important as it provides a way to systematically identify the molecular basis of most childhood cancers. We are now able to prise open the lid of the black box of this previously poorly understood collection of diseases.”
ZERO has helped children like Thomas, who was diagnosed at two years of age, with a rare form of brain cancer. Thomas’ condition was deteriorating, and after undergoing multiple surgeries and losing much of his eyesight, the treatment options were quickly running out. Once Thomas was enrolled in ZERO, a rare mutation driving his cancer growth was found, and a new experimental drug was identified to target it. He had a dramatic response to this treatment with shrinkage of his tumour. Today Thomas is eight years old and whilst he is still receiving his therapy, his future looks bright. He is back at school and able to return to the activities he enjoys.
For some children, whilst ZERO was not yet able to provide a total cure from their cancer it has brought them the chance of an extended life. Three-year-old Stella suffered from an extremely aggressive brain cancer that meant she could no longer talk, walk or eat unaided and was in palliative care when she was enrolled on ZERO in 2017. A genetic driver was identified in her brain tumour, and when she received the recommended targeted therapy her tumour regressed completely – she became well enough to run around and play like any healthy child. Sadly, after 10 months of treatment, her tumour grew back and she passed away. Whilst ZERO could not save Stella, it was able to prolong her life, giving her 10 months of happy and relatively healthy time with her family, that they otherwise would not have had.
The ZERO program aims to give all Australian children and young adults diagnosed with cancer access to treatment plans tailored to their individual cancer.
Thanks to $67 million in new funding announced in April 2020 from Minderoo Foundation and the Australian Government’s Medical Research Futures Fund to scale the ZERO program, the potential of these promising early results could benefit 1,000 children and young people per year by end 2023.
Dr Steve Burnell leads Minderoo Foundation’s Collaborate Against Cancer initiative, which has a goal to make cancer non-lethal in this generation.
“Minderoo Foundation is proud to partner with the Australian Government to help make the potentially life-saving insights generated by the ground-breaking ZERO program available to every Aussie kid diagnosed with cancer,” he said.
“The children enrolled in ZERO to date have received the devastating diagnosis of a cancer that is extremely aggressive or have been told there are no more treatment options available to them. These very exciting results, published in the world-leading Nature Medicine journal, indicate that the ZERO program can provide improved outcomes even in these very sick kids who have been given a 30 per cent or less chance of survival.”
The collaborative program, led by Children’s Cancer Institute and the Kids Cancer Centre at Sydney Children’s Hospital, connects a powerful network of researchers and clinicians across all eight of Australian children’s hospitals and 23 national and international research centres, and has established the country as an international leader in paediatric precision medicine.
While this data published in Nature Medicine reports on the first 250 patients of the national clinical trial, ZERO has now enrolled close to 400 children.
“ZERO represents a new paradigm in the management of paediatric cancers. Minderoo Foundation is pleased to support the program’s expansion so that all Australian kids diagnosed with cancer might benefit from the beacon of hope ZERO represents to Australian families facing that shattering moment of a childhood cancer diagnosis,” Dr Burnell said.
Established by Andrew and Nicola Forrest in 2001, we are a modern philanthropic organisation seeking to break down barriers, innovate and drive positive, lasting change. Minderoo Foundation is proudly Australian, with eight key initiatives spanning from ocean research and ending slavery, to collaboration in cancer and community projects.