Demystifying medulloblastoma

Demystifying medulloblastoma

​Prof Wainwright (just call me Brandon) is discovering better treatments for brain cancer. 

Prof Wainwright (just call me Brandon) is the Director of the Institute for Molecular Bioscience at The University of Queensland. The Kids’ Cancer Project is currently funding a study he’s leading to discover better treatments for medulloblastoma (a type of brain tumour) while reducing the toxic effects of it. We caught up with Brandon to find out more.

What’s the current treatment of this type of brain cancer?
The current cure rate for medulloblastoma is 50 per cent, and it’s treated with surgery (to remove the tumour), radiotherapy and cycles of chemotherapy. The problem with radiotherapy and chemotherapy is that they work by killing growing cells, and in the patient’s body it’s not just the tumour that’s growing. You can think of it as like using weed killer.

How do weed killers work?
Well, it works because weeds grow faster than grass. Chemotherapy and radiotherapy don’t completely discriminate, they just mostly kill the thing that is fastest growing – in this case, the brain tumour but there is an effect on normal cells that are growing as well. The trick is to target the radiotherapy and keep a close eye on the doses and side effects of both the chemotherapy and radiotherapy.

That does sound toxic. What are some of the side-effects?Unfortunately, some children will develop learning difficulties. Another side-effect is neuropathy - a nerve condition that can lead to pain, and loss of function in different parts of the body.

Read more: New therapies for incurable paediatric brain tumours.

The study you’re doing is to test an already approved drug that targets defective proteins in the cancer cell. How is this going to work differently to chemo?
Over the past year we identified the core genetic components that lead to the development of medulloblastoma. It was no mean feat, as the genetic network is incredibly complex. We had to search for the one critical circuit that controls the growth of the tumour but not in the normal cells. Once we found that, our hypothesis was that we’d be able to find a drug that would act as the circuit breaker.
So you found the drug?
Yes. Our repurposing strategy uncovered a drug that was originally developed to treat breast cancer.
Did your hypothesis work? Is that drug the circuit breaker?
We’ve tested it in mice bearing human tumours, and yes, it worked. Over a period of 20 days, our study showed 100 per cent survival and tumour shrinkage that was quite amazing. But in cancer, there’s no such thing as a magic bullet. And as soon as we stop the drug, some of the cancer comes back. You have to smack cancer from all different directions to fight it. This one particular drug does a great job, but it would be enhanced in combination with other therapies, like chemo. We have an 18-month plan to test complementary chemo and then get it into clinical trial.
What’s next?
We are going to try and answer what we believe to be the single most overlooked question in cancer research, particularly in paediatric brain tumours.
Sounds big.
It is. I’m working collaboratively with other researchers funded by The Kids’ Cancer Project such as Dr Nick Gottardo and also Professor Michael Taylor of Sickkids (The Hospital for Sick Children) in Toronto. The question we asked was, why do we focus on the current cancer, when it’s a recurrent or metastatic cancer that ends up being fatal? 

Read more: In Focus: Institute for Molecular Bioscience.

Good question. We hear time and time again, ‘the cancer came back, and there was nothing that could be done.’
What has been discovered is that the exact same cancer doesn’t come back – it’s highly related and it might look similar to the first one, but it’s not necessarily. That’s why it is unlikely to respond to the same therapy. It grows and changes – cancer is like a criminal let lose in a village – they’re completely lawless having broken one law and don’t behave in any conventional ways.
What’s the answer?
There are a lot of answers needed for a big question. One is to do a very comprehensive genetic analysis comparing primary to recurrent cancer from the same patient and pair it with new genetic approaches. For example, there’s been a very exciting development called liquid biopsies. What has been discovered is the DNA of cancer cells can be found in the blood or spinal fluid in the case of brain tumours. So we can now do ‘liquid biopsies’ and look at the cancer DNA to see how it’s changing and adapt therapies to suit.
Science is incredible!
Science is a long process, but we are making headway. It’s all about asking a hard question, getting an interesting answer – discovering something, then committing to innovate and getting the results of the research to the patient.
Thank you for sharing this update with us Brandon, we’re so inspired by what you do.
Thank you for having me. We quite literally couldn’t do it without funding from The Kids’ Cancer Project and the generosity of all your donors.