A new way to attack cancer

A new way to attack cancer

Associate Professor Alex Swarbrick’s research has revealed that neuroblastoma, a childhood cancer occurring in the abdomen, is particularly dependent upon microRNAs.

The treatment of childhood cancer could become far less damaging and invasive if Associate Professor Alex Swarbrick and his team continue to hit home runs.

It is so terrifying that it’s almost unthinkable to imagine a toddler receiving high-dose chemotherapy, said Swarbrick. As a result of such treatment, many youngsters lose their hearing, either completely or partially. They can develop major skeletal issues and other problems. They are also at higher risk of other cancers later in life.
“This is all just so unfair,” Swarbrick, a Laboratory Head at Garvan Institute, said. “This absolutely motivates me in terms of the potential of the impact of my team’s work. If we can spare even a single child from suffering high-dose chemotherapy, then that’s enough to drive us forward.”
The research, funded by donations to The Kids’ Cancer Project, is focusing on a class of genes known as microRNAs. While most genes provide instructions to make a protein (for example, one gene makes collagen, the body’s most abundant protein, which provides skin with structure), microRNAs instead make RNA molecules. MicroRNAs modulate and control the activity of other genes.
Swarbrick’s research has revealed the fact that neuroblastoma, a childhood cancer occurring in the abdomen, is particularly dependent upon microRNAs.
“That has led us to wondering whether microRNAs could themselves be used as a drug to treat neuroblastoma,” Swarbrick said. “The story began almost 10 years ago when we discovered a microRNA that had a potent effect in human stem cells."

"When we went looking for a cancer in which this microRNA might function, we found neuroblastoma to be one of the few human cancers where this microRNA is very important.” 

“Then, with the support of The Kids’ Cancer Project, we said that if there is one of these, maybe there are more. So we have done extensive experiments to test the effect on neuroblastoma of every single microRNA that human cells can produce."

"That process has turned up several more microRNAs that also seem to be critically important to the survival of neuroblastoma cells," he said. 
Best of all is the news that the path to making a drug, once researchers are confident they’ve found a microRNA that could be used as such, is mercifully short.
In the traditional cancer drug discovery process, researchers find a protein that is essential for the cancer cell. Then they must endure years (often at a cost of billions of dollars) of drug discovery, to find a molecule that fits into that protein and stops it from working.
But a microRNA-based drug would be a nucleic acid, which can be directly synthesised. This means the drug discovery phase could be skipped, with researchers instead jumping directly into early-phase clinical trials.

“Once we are convinced in experimental models that the microRNA has the potential to be a valuable treatment for neuroblastoma, we can move quite rapidly,” Swarbrick said.

“Quite nicely, the first evidence that a microRNA can work as a drug for cancer came from Sydney quite recently. A group showed that a microRNA-based drug can be used to treat lung cancer."

"That was a world first and it provides local evidence that you really can go from lab-based discoveries and jump quickly into potentially successful, early-stage trials.”

A faster move into human testing could mean that less young children will suffer the physically nasty and potentially damaging effects of high-dose chemotherapy treatment.
Another exciting point about microRNAs is that they’re in a new and relatively unexplored space. Researchers must constantly test fresh ideas and explore new areas in order to stand a chance of making a real difference.
Without essential funding made possible by donations to The Kids’ Cancer Project, Swarbrick said, such new discoveries would not be possible.
“The Kids’ Cancer Project fills an important space for us in providing seed funding for new ideas,” he said. “Conventional funding mechanisms, through the government for example, are quite conservative. This is understandable, to a degree. Such mechanisms often need years of preliminary evidence to be sure that what they’re funding is going to result in a home run. But of course, you need funding to get that preliminary evidence.”

“The business world has angel investors or seed funders to help kickstart an early-stage business. The children’s cancer research world has The Kids’ Cancer Project.”

Just as those small businesses funded by angel investors can grow up to become major, multinational corporations worth billions of dollars, the work being done by Swarbrick and his team could change the way we view the treatment of certain cancers and eventually have a positive outcome for thousands of seriously ill children around the globe.
“I regularly see The Kids’ Cancer Project doing this job around the country,” Swarbrick said. “As a researcher who knows how difficult it can be, I’m amazed at how many projects they’re supporting right now, and how diverse those projects are.”
“From fundamental, lab-based research, right through to clinical trials, The Kids’ Cancer Project is supporting a lot of vital, exciting, innovative work. They’re helping researchers to move quickly and aggressively to pursue new ideas that we hope are going to make a real difference.”


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