Newcastle Herald: Hunter research team led by Dr Matt Dun find two drugs are better than one in lab tests on DIPG
IT WAS the “eureka” moment Dr Matt Dun had been waiting for – his team had found a promising way to buy more time for children with DIPG.
But the discovery was somewhat bittersweet.
While it had the potential to improve outcomes for children and families fighting diffuse intrinsic pontine glioma, it came too late for the Hunter researcher’s own little girl – four-year-old Josephine – who lost her battle with the ferocious brain stem cancer in December.
“When we saw the results – that the cells were turning on in response to the drug, and that we could use the other drug to turn it off – it was like, ‘Eureka!’,” Dr Dun said.
“Then it was, ‘Damn, why didn’t we do this at diagnosis? Why did we wait until 14 weeks after she progressed into advanced stages to try it?’ It is nice that things are working, it is just a pity we didn’t have this data two years ago.”
Two of Dr Dun’s team members – Dr Ryan Duchatel and Evie Jackson – were working on separate drugs to treat DIPG at their University of Newcastle, Hunter Medical Research Institute lab, and both individual studies were showing potential to improve outcomes, at least marginally. But they soon discovered the drugs worked better together. That there was a “synergistic” effect. Eureka.
“With Ryan’s project we treated DIPG cells with the drug and measured what happened to the cells to work out how they evaded response,” Dr Dun said. “But then Evie was doing work on this known drug that was in clinical trials, but nobody knew how it worked – and that’s why I didn’t get it for Josie initially.
“Once Evie figured out that the sensitivity of the cells had no correlation with what was previously known about the drug in other cancers, I got on a plane to Germany to get my hands on it, because there was hope it could work for Josie.”
Dr Dun said while it had worked in the lab, they had to be cautious about building too much hope as it was early days.
“Hopefully it means these kids will get a bit longer – and I think it is only going to be a bit,” Dr Dun said. “I don’t think this is the silver bullet.
“Of course we don’t know if it will work, but I feel good about it. Now we wait for the results of the animal study.”
The next phase of the study should begin in a London lab within the next two-to-three weeks.
Dr Dun spoke about his team’s promising research ahead of DIPG Awareness Day on May 17, when his family-run charity, RUNDIPG, would launch a virtual running festival – Bolt For Gold – to raise money to help fund this important research.
South Sydney and NSW Blues dummy-half Damien Cook is an ambassador.
Due to COVID-19 measures, Dr Dun’s team has been unable to take their findings from the lab into animal studies in Australia. They needed to send samples to a lab in London for testing at a cost of $137,000.
“That’s a lot of running,” he said. “DIPG kills one-fifth of all kids in Australia with cancer.
“We say it’s rare, that it only affects 20 kids in a year, but it kills one-fifth of all kids. And there is no treatment, so there is no hope.
“You want to have some hope, right? It is pretty devastating regardless. But not knowing what to try, not knowing where to go, or what to do, is just not fair.
“For me, I thought, if we can do something about this… at the end of the day we lost our little girl, but we have gained a lot of information that we hope will help other families of kids with DIPG.”
Dr Dun said his whole team had been “incredible”.
“They haven’t wavered in their enthusiasm,” he said. “It’s all well and good to have skills and knowledge and the ability to learn, but staying motivated is crucial.
“The fact we have been able to do so much in so little is a credit to them.
“We understand the mechanisms now, so there should be other drugs we can combine together that should do the same thing, or have a similar effect. This idea that rather than targeting the gene mutations of a tumour, but targeting how they respond to the environment of the tumour – whether it’s high oxygen or low oxygen – targeting those pathways simultaneously deprives the tumours of their energy, and that has a synergistic effect.
“We are always restricted by what pathways we choose for DIPG because we have to get drugs into the central nervous system. We know that it kills the cells in combination together really well, regardless of whether there is oxygen or no oxygen.”