Professor Michelle Haber is executive director of Sydney’s Children’s Cancer Institute and a professor at the school of women’s and children’s health at the University of NSW.
June 30, 2021
To say that every child’s cancer is unique to them sounds like a no-brainer, until the revolutionary implications of that statement are made clear by biomedical researcher and Michelle Haber, a mission-leader in what she calls “the most comprehensive child cancer precision medicine program in the world”.
“There’s about a thousand children and adolescents diagnosed every year with cancer,” the University of NSW professor and executive director of the Children’s Cancer Institute in Sydney says.
“Current survival rates for kids with cancer are, overall, about 80 per cent and that’s increased dramatically from 50 or 60 years ago when virtually every child died of cancer,” Professor Haber says. “That improvement has effectively been brought about by a combination of chemotherapy and the multidisciplinary approach to treatment, but it’s pretty much plateaued over the last 20 or so years.
“So the advent of precision medicine, matching the genomics and biology to the right drug at the right time is the next new inflection point in these curves that we believe has the capacity to take that survival rate one day up to 100 per cent.”
Since 2017, the Zero Childhood Cancer Precision Medicine Program, a joint initiative of CCI and the Kids Cancer Centre at Sydney Children’s Hospital, has enrolled more than 500 children and adolescents with a less than 30 per cent chance of survival in its national precision medicine trial, with outstanding results.
While there have been multiple sources of funding, ZERO has received substantial federal investment, including $5 million from the federal government’s Medical Research Future Fund (MRFF) in 2018 and a further $54.8m through the fund last year. That funding, together with $12.2m from the Minderoo Foundation, was to make the trial available to all Australian children and adolescents dioagnsed with cancer, irrespective of type, stage, or risk, which will be up to 1000 per year by the end of 2023.
The precision medicine trial established a platform on which data about the tumour tissue of every child with high risk cancer could be collected and analysed and “tested against a battery of potential therapeutic treatments”, Haber says.
“We would also implant them into avatar mice so we could grow the tumour and then treat the child’s cancer in a living organism to see which particular treatments that child might respond to most effectively.”
The results for the first 250 children demonstrated the power of the genomic platform. In more than 90 per cent of cases the researchers were able to identify the genetic or molecular driver of the disease; in more than 75 per cent they were able to make a personalised treatment recommendation; and in those children who received the recommended treatment, 70 per cent either had a complete response, a partial response, or their disease was stabilised.
“What precision medicine says basically is forget the traditional categories of types of tumours – let’s do very extensive and detailed genomic analysis of these children’s cancers, find out what genes are active, which genes have been modified and whether there is a treatment that targets it,” Haber says.
“When we do that we may find the same genetic rearrangements in a child that has a brain tumour as in a child who has a tumour of the soft tissue sarcoma, for example. And so we now know that we can treat children with completely different pathological classifications of their tumour with the same drug because we’ve identified the specific genetic change that is driving that child’s cancer.
“So it’s really turning the model of care on its head and saying, let’s use these new tools to treat children more smartly and more effectively.”
Haber has high hopes that the same approach might improve outcomes for the 80 per cent of child and adolescent cancer patients who currently survive, but live with the terrible side effects of usual treatments.
She says these are “mostly old drugs that have been around since cancer treatment was first discovered in the 1940s and 50s”. Among the dangers are heart and other organ damage, metabolic disorders such as diabetes and conditions such as deafness; or even second cancers unrelated to the original cancer. “About two-thirds of them have a lifelong chronic health condition and in a third of these, this can be serious or life threatening,” she says of young patients.
One standout success story is Ellie Caterjian, who was eight months old in 2017 when she was placed on the ZERO clinical trial after a large tumour in her chest resisted standard treatment. Her tumour was sequenced and the genetic abnormality discovered. Her doctors tracked down a US pharmaceutical company which made a drug that specifically targeted the abnormal protein being produced, and donated it on compassionate grounds. Four weeks later Ellie was off life support, a fortnight after that she was moved out of ICU.
“It was a syrup, like Panadol, you take on a spoon,” Haber says. “No side effects, absolutely nothing that is damaging anything in the child except for the tumour.
“Imagine if we were able to do that for all of these children –– identify the smart drugs that can treat them, not give them this pot pourri of poisons.”
Another discovery when the ZERO scientists analysed the data on that first cohort of 250 patients was that 16 per cent of the children had a genetic predisposition to cancer.
“That’s the highest incidence of cancer predisposition genes that’s been seen anywhere in the world, about double what’s been reported anywhere — as a result of the sophistication of our genetic tests.
“We’re sharing our data internationally so quite soon we’ll have aggregated thousands of child cancer genomes in the cloud for international analysis, unprecedented power to find new discoveries.
“We want to set up a national child cancer predisposition program. This is the path ultimately to screening, and potentially for prevention of tumours that haven’t yet appeared. The opportunities for new discovery, for new ways of using the data and improving outcomes is beyond anything I’ve ever seen in my professional career.”