Behind the science: Professor David Ziegler

Behind the science: Professor David Ziegler

Leading Australian scientist and paediatric oncologist has made it his goal to find a cure for a cancer that currently has no treatment, and he’s making excellent progress.

When Associate Professor David Ziegler picks a fight, he sure does pick a fight. Not content with advancing the science behind cutting-edge therapies to treat children’s cancers in general, Ziegler decided to take on the single most aggressive cancer.

Diffuse intrinsic pontine gliomas, known more commonly as ‘DIPG’, are tumours typically found at the base of the brain. Tragically, for those suffering the cancer, there is no effective therapy. It is incurable, but Ziegler aims to change that.

“It’s a devastating disease,” says Ziegler, a paediatric oncologist and Senior Staff Specialist at Sydney Children’s Hospital.

“It strikes young, healthy children. The typical incident occurs at around five to seven years of age, to children who are otherwise perfectly healthy. They have a very short duration of symptoms when we find the tumour and we know, once it’s found, that the cancer is incurable.”

Group Leader of the Brain Tumour Group at Children’s Cancer Institute, Ziegler and his colleagues have screened thousands of drugs to find something that could have an effect on the aggressive cancer.

The fact that they’re finding it so difficult to solve, he says, reflects the veracity of their research.

“If we seemed to be finding solutions too easily, we’d know that our modelling didn’t accurately reflect the clinical situation where the disease is so hard to treat,” he says.

Why did Ziegler choose such a challenge? One reason is that nobody else was doing the research, so somebody had to.

“Mostly though, I was motivated by patients and parents we had in the hospital,” Ziegler says. “The worst conversation you can have with a parent is to tell them there is no treatment for their child. So those patients and parents motivated us to start the research program and begin to try to make a difference.”

And, in fact, it’s not a hopeless quest. “It feels as if, with DIPG, we are where leukaemia was 50 years ago,” he says. “When I first proposed to other scientists that this would be a good disease to study, many hadn’t even heard of it.”

“It is in such a critical, delicate part of the brain that surgeons can’t operate and remove it. That meant there was a lack of tissue in the lab for scientists to study.”

Now, partly thanks to Ziegler’s pioneering work that began eight years ago, parents are donating their children’s tumours to science after the child dies. That, in itself, was a major challenge. Then, the real work began.

Part of the problem, he says, is that prior to this program, researchers had been operating in the dark. Without tumour samples to guide the research, it has been close to impossible to discover which drugs might be more likely to succeed.

Some of the research projects funded by The Kids’ Cancer Project, carried out by Ziegler and his team, include screens of thousands of drugs by robotic technology, to find anything that will kill DIPG cells. This has resulted in the discovery of an anti-malarial drug that is active against DIPG.

Another program is investigating the immunotherapy pathway, which harnesses the individual’s immune system to launch an attack on the DIPG cells. This project is looking into specific genes that can be switched on and off by targeted agents to regulate cell deaths.

“There’s one drug we’re very excited about that works by targeting the cell cycle,” Ziegler says. “The cell cycle is the machinery that allows cells to continually grow and reproduce. What we’ve found is a drug to which the cells are exquisitely sensitive. It’s a very active drug, and it’s able to penetrate into the brain.”

“We’re working with a company that has developed a new formulation of this drug that gets into the brain even more efficiently. So, we’re about to test that, to work toward a clinical trial.”

These programs only exist, Ziegler says, because of donations from the community. The research lives and dies on such support.

“We get grants from the government, but they make up only a fraction of the funding we need to do this work,” he says. “We have only got to the point we’re at now because of community donations and funding from groups such as The Kids’ Cancer Project.”

“It’s important to understand that we will get there, just like researchers did with leukaemia. The current success with leukaemia didn’t happen overnight. Scientists learnt from each child who responded well in clinical trials over the decades, and eventually built up to a 90 per cent survival rate. But they had to start somewhere. That’s what we’re doing with DIPG.”