Children with high-risk cancers have received effective treatments leading to complete or partial regression of their cancer thanks to a pioneering research program that tailors therapy based on the complete DNA sequence of a patient’s individual tumour.
A report of 247 participants of the Zero Childhood Cancer Program published in the prestigious scientific journal Nature Medicine, has revealed that over 70% of participants could be recommended a personalised treatment option based on a full scan of the genetic makeup of their unique cancer. Of those children who received a targeted therapy based on this DNA information, one third went into partial or complete remission.
Adding DNA scans of the children’s tumours to the other cancer analyses performed in the Zero Childhood Cancer Program was made possible through the Lions Kids Cancer Genome Project. This project partnered the Zero Program, led by the Children’s Cancer Institute and the Kids Cancer Centre at Sydney Children’s Hospital, with the state-of-the-art genomics at the Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, thanks to $4M funding from the Lions Club International Foundation and community fundraising by the Australian Lions Childhood Cancer Research Foundation and Lions Clubs across Australia.
Dr Joe Collins, Chairman of the Lions Kids Cancer Genome Project, says: “We are thrilled to have invested in this visionary project. To see it make such a difference for kids that have no options left is truly remarkable. The legacy that this project has left is that we’ve not only saved a number of children, we’ve helped establish a database that is going to help kids all over the world. Without Lion’s ’funding, this project may not have happened.”
“This milestone highlights the power of community support to drive life-changing research outcomes for patients that have few other options left,” says Prof Marie Dziadek, Garvan’s Chief Scientific Officer and coordinator of the Lions Kids Cancer Genome Project. “The findings will be shared across the globe to benefit countless children worldwide.”
A new approach to cancer therapy
Every year, over 950 children and adolescents in Australia are diagnosed with cancer. Of these, three die each week. Despite major advances in therapies, cancer remains the leading cause of disease-related death in children in most developed countries – in large part because every cancer is unique and clinicians can’t be certain which treatment will be effective in which child.
A collaborative team of researchers and clinicians set out to change the outcomes for children with aggressive cancers. Researchers at the Children’s Cancer Institute and Garvan, and other collaborating organisations, came together with paediatric oncologists at the Sydney Children’s Hospital to form the Zero Childhood Cancer Program – a precision medicine program aimed at using the power of genomics to identify a personalised treatment strategy for each child.
Through work initiated by Dr Marie Wong and A/Prof Mark Cowley at Garvan’s Kinghorn Centre for Clinical Genomics in 2016, the program employed a cutting-edge diagnostic pipeline: conducting sophisticated genomic profiling of the children’s unique cancers, and then matching them with a treatment that was most likely to target their individual tumour.
From small change to big impact
National rollout of the Zero Childhood Cancer program – and the ability to sequence the cancer genome of hundreds of children – required significant investment.
This need was met by the commitment and passion of the Lions Club International Foundation, the Australian Lions Childhood Cancer Research Foundation and Lions Clubs around Australia.
In May 2016, Lions launched the Lions Kids Cancer Genome Project, which had the ambitious goal of sequencing the genome of tumour samples from 400 children and was spearheaded by Prof Dziadek and Prof David Thomas, Head of the Genomic Cancer Medicine Lab at the Garvan Institute and Director of The Kinghorn Cancer Centre.
Through global and local fundraising, including a grass-roots drive that appealed to Australians to collect spare change to support the pioneering cancer research, Lions raised a significant $4 million for the Lions Kids Cancer Genome Project. This crucial investment made it possible to sequence the 400 tumour samples, completing a major milestone in 2020.
Treatment guided by genomics
The Zero Childhood Cancer Program led to an unprecedented sharing of Australian genomics expertise. Dr Wong and A/Prof Cowley joined the Children’s Cancer Institute in 2018 to continue the Zero Childhood Cancer Program and develop the Institute’s genomics capability. The project was further enhanced by RNAseq analysis performed at the Murdoch Children’s Research Institute.
This world-leading collaboration had life-changing outcomes for children in the Zero Childhood Cancer Program who had initially received a poor prognosis. One of the program’s early successes was Ellie, a young girl who was diagnosed with a rare cancer in her chest at only 11 months. Her tumour was successfully treated with a drug recently developed by a US pharmaceutical company, which she received on compassionate grounds.
But Ellie is not alone. Data from the first 247 children enrolled in the Zero Childhood Cancer Program showed that the genetic basis of a child’s cancer could be identified in more than 90% of cases and 70% of patients had at least one new potential treatment option identified based on their cancer’s genetic makeup.
Results showed that in 30% of those treated with personalised therapy the tumour shrank and in some patients completely regressed. In another 40% of cases, the tumour stopped growing and stabilised.
This early success of the program has attracted further significant funding. The Australian Government recently announced a major grant of $54.8 million that together with additional support from the Minderoo Foundation will ensure every child in Australia diagnosed with cancer will have access to genomics-guided precision treatments through the Zero Childhood Cancer Program.
A lasting legacy for childhood cancer
While the program has been life-changing to many patients and their families, the reported study will provide a valuable resource for childhood cancer for clinicians and researchers across the world, as they continue working to find cures and improve the outcomes for children with cancer.
Prof Thomas, who is a co-author of the paper published in Nature Medicine, says: “We’re in one of the most exciting periods in the history of cancer treatment. It’s an era when for the first time we’re able to use science to understand what is going on in the patient and use that information in real time to make a difference to their lives.
“All of that has become possible because of the technology that Garvan acquired six years ago, through the generous support of the Kinghorn Foundation in the establishment of the Kinghorn Centre for Clinical Genomics, when it became the third site worldwide to acquire the capacity to sequence more than 10,000 whole human genomes a year. The Lions Kids Cancer Genome Project has added enormous value in understanding why children and young adults develop cancer and what we can do about it in the longer term. I see that as part of the long term strategy to try to improve cancer survival.”
Prof Dziadek adds: “The dedicated collaboration of researchers, clinicians and, crucially, the community’s generous philanthropic support has made this project happen. The Lions Kids Cancer Genome Project, powered by philanthropy, has enabled Garvan’s capability in genome sequencing to contribute to the success of the Zero Childhood Cancer Program. This has not only changed the lives of children with cancer today, it will inform future research needed to defeat these cancers tomorrow. In the coming years, as the program rolls out, all children diagnosed with cancer will have greater hope of a bright future.”