Hunter researchers have discovered a drug combination that is showing promising signs of improving the life expectancy of children with aggressive brain cancer.
A team of researchers, led by University of Newcastle cancer researcher Professor Matt Dun, made the breakthrough.
Professor Dun has devoted his life to researching new treatments for DIPG (diffuse intrinsic pontine glioma), a childhood cancer he described as a "terrible monster".
The disease took his daughter Josephine's life at age four in December 2019.
The breakthrough, which involves the university and Hunter Medical Research Institute, has been achieved in five years - eight years faster than expected.
Professor Dun's team pinpointed a mechanism in the brain tumour that was evading the anti-cancer effects of a promising oral drug named "ONC201".
The drug is currently used in a dozen clinical trials worldwide, across many cancer types.
This includes the most lethal childhood cancers - DIPG and DMG (diffuse midline glioma).
One of these trials is occurring in Newcastle, across Australia, the US, Netherlands, New Zealand and Switzerland and will soon extend to other countries.
It uses ONC201 in combination with another drug called paxalisib. The trial was established using preclinical data generated by Professor Dun and his team.
ONC201 has been shown to extend the lives of DIPG patients from about 11 months to 20 months.
Professor Dun described the drug as a "tiny molecule that gets across the blood-brain barrier".
This barrier stops infections like viruses and bacteria - as well as toxins - travelling from the circulation into the brain.
"That's the biggest obstacle to increasing survival of brain cancer patients," he said.
That is, establishing oral drugs that can travel "from the stomach to the brain".
"Typically they get taken up by the liver and secreted as toxins," he said.
ONC201 was discovered in 2016, but it was unclear how it worked.
In 2018, Professor Dun's team tested the drug in the lab and discovered its characteristics.
Cancer cells in the brain were being damaged by the drug, but "the cells were smart enough to upregulate other pathways that led to their survival".
Professor Dun's daughter Josephine was diagnosed with DIPG in February 2018.
Dr Dun examined a biopsy of his daughter's tumour and determined that the cancer cells were dependent on one of these pathways for their growth.
"I knew I had to find a drug that gets into the brain that targets that pathway," he said.
He searched the world and found the oral drug paxalisib being used in a clinical trial for adults with glioblastoma brain cancer.
The drug had been bought by Australian company Kazia Therapeutics, based in Barangaroo in Sydney.
"I contacted the CEO, he drove up the M1 motorway and we had a meeting in my lab."
He allowed Professor Dun to test the drug against DIPG tumours. It showed promising results.
His daughter became the first child in the world to trial paxalisib in combination with another drug for three months, which stabilised her tumour.
When the tumour returned, she was given the combination of paxalisib and ONC201.
She lived more than a year beyond the standard prognosis for DIPG patients.
Then, about 18 months after she passed away, an international clinical trial began using the drug combination discovered by Professor Dun's team.
Professor Dun said 101 children are now involved in the trial, with some patients showing promising results.
Two girls in Sydney are part of it. They have survived almost three years after diagnosis while on the drug combination, a dramatic extension on historical survival of less than 12 months.
"That's good survival without serious side effects," he said.
Professor Dun is on a mission to keep improving treatments as a legacy to his daughter, family and supporters - including his RUN DIPG charity.
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