As a child, Associate Professor Geraldine O’Neill’s favourite television program was The Curiosity Show. She particularly enjoyed the segment titled, ‘Why is it so?’.
Now, as a brain cancer researcher, it is O’Neill’s rampant curiosity that has seen her sail into uncharted territory by asking herself that very same question.
“When I first started out in the field, I wondered why the more deadly forms of brain cancers were more invasive around the brain tissue,” said O’Neill, Group Leader of the Focal Adhesion Biology group and Conjoint Associate Professor at the University of Sydney.
She believes that with a greater knowledge of the distinctive environment of the brain, researchers are more likely to develop treatments that boast not only a greater success rate but also a kinder treatment process.
L-R: Associate Professor O’Neill, PhD student Victoria Prior and PhD student Amy Sarker aim to use new technical approaches to ‘print’ brain tumours in gels with the same soft consistency as brain and, separately, to grow ‘mini-brains’ from human stem cells.
“Laboratory tests that researchers come up with involve new ways of treating brain cancer, but they are using approaches that don’t consider the environment that the cancer finds itself in once it’s in the patient’s body,” O’Neill said.
“Brain cancer is interesting because it’s a disease that’s difficult to cure as it is not united by common mutations, so it’s got a very heterogeneous genomic landscape and can’t be tackled like other forms of cancer.”
Stacking the odds towards success
One of the major problems in the field of brain cancer research, she said, is that historically there has been a very low success rate of clinical trials.
This is particularly true of high grade glioma brain cancers, which are highly aggressive and one of the most difficult to treat. At the moment, there are very few treatment options available for a child who is diagnosed with this cancer.
However, O’Neill’s research shows that some glioma drug targets respond differently using standard laboratory tests as opposed to new tests that better replicate the landscape of the brain.
“Some treatments look good in the lab. But once they go to clinical trial, they’re just not working,” O’Neill explained.
“The work that we do is designed to mimic the patient’s body in the lab, because we believe that this is going to be the way to discover better results for patients.”
That is why O’Neill’s new research project, partly funded by The Kids’ Cancer Project, is so important.
Her team is employing new technologies to ‘print’ brain tumours in gels that have the same “tofu-like” consistency as the human brain. Separately, the team will grow ‘mini brains’ from human stem cells. Armed with these tools in the lab, researchers will be better able to measure the potential success of various brain cancer treatments and therapies.
Along the way, a large amount of resources, effort and money should be saved in the avoidance of clinical trials that are less likely to succeed.
Science for the scientists
O’Neill and her team are now at the forefront of the battle against brain cancer and theirs is a two-pronged attack.
“Firstly, we are using these models because we want to find better treatments. But secondly, we hope that by sharing the information we discover with the scientific and medical community, they’ll begin incorporating similar kinds of methods in their own research.”
On their journey into the human brain, O’Neill and her team are not only using ground-breaking technologies, they are also collaborating with different disciplines in order to gain greater insights into the disease.
“We’ve been working with biophysicists because it’s increasingly understood that cancer cells have receptors that allow them to sense forces in their extracellular environment, and that can influence the biochemistry of the cell,” she said.
“We also collaborate with tissue engineers, people who are interested in building tissues in culture dishes in a lab.”
Further technical advances in medical knowledge have aided her team in their vital research. For example, in the past, cancer cells from some glioma patients have been difficult to obtain as a biopsy was difficult and dangerous to perform. However, advances in research mean doctors are beginning to biopsy.
“Surgical approaches have improved with time meaning it’s safe to biopsy a glioma patient,” O’Neill said. “Now, we have the capacity to grow cell lines that we can use in the lab.”
Although O’Neill admits her journey into the human brain has only just begun, she believes that compared to when she began working in brain cancer research, less than a decade ago, “there’s every reason to hope that we’re in a really good place at the moment, developing approaches that will allow us to better predict the likely success of treatments in patients.”
It’s bold science that has in its sights a major improvement in the results, and the side-effects, of brain cancer therapies in children.
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