Breaking down barriers

What inspired you to pursue a career in paediatric oncology, and how did you transition from being a clinician to a researcher?

My passion for science began early, thanks to a summer camp called “Having Fun with DNA” my parents enrolled me in just before I entered 7th grade.

I remember thinking ‘it’s the summertime, what in the world do they have me doing, going to this science camp’. But it was a transformative experience that sparked my curiosity in asking scientific questions. Later, I realised that I’m a people person and have a love for both research and interacting with people, which led me to pursue both MD and MDPHD programmes.

While in the end I trained as an MD. I still retained a love of research and passion for science. While I knew I wanted to be a clinician, I also knew that it was important to be able to ask questions around the treatments we give, why we give them and how well they work. First, I trained as a paediatrician, then specialised further with fellowships in haematology-oncology and paediatric neuro-oncology and clinical pharmacology.

This combined clinical and research focus now drives my work in running clinical trials and leading a lab focused on paediatric brain cancer.

That’s how I came to be where I am today, caring for patients, running clinical trials for brain tumour patients and leading a lab centred on brain cancer research.

A lot of your research focuses on the blood-brain barrier. Can you share some insights into what your research has revealed about this?

So, the blood-brain barrier (BBB) is a selectively permeable collection of cells which acts as a ‘preventative wall’ regulating the entry of molecules into the brain. While it protects the brain from toxins, you could say the issue comes as it restricts the delivery of potentially life-saving therapies to aggressive brain tumours and areas around the tumour.

Our research aims to temporarily open the BBB to enhance drug delivery directly to the tumour cells while ensuring it closes again to reduce toxicity for the rest of the body. We’ve seen some success in preclinical and animal models, where we were able to transiently open the BBB and increase chemotherapy delivery to the tumour site. Now, we’re working to translate these findings from bench to bedside.

What new research techniques are you most excited about in terms of understanding childhood brain tumours like glioma and medulloblastoma?

Molecular testing is incredibly promising. While it’s not entirely new, it allows us to tailor treatments to individual patients based on their specific genetic profiles, hopefully making them both less toxic and more effective.

I’m also excited about the potential of 3D printing technologies; it’s being used more and more in this field to create things like brain-on-a-chip and brain cancer-on-a-chip. This allows us to create models of brain tumours and carry out dynamic imaging. We can even and look at their vasculature and perfuse it just like you would a blood vessel in the brain -helping to study drug delivery in real-time and understanding timing and dosage. Hopefully this could significantly accelerate our ability to translate lab discoveries into clinical treatments.

Have you found that a CNS tumour impacts the molecular makeup of the BBB to be more or less “leaky” in people with tumours compared to those without?

Yeah, I’m glad you asked that. For certain tumours like glioblastoma, there’s a big difference in how the blood-brain barrier behaves. In the core of the tumour, the BBB is very leaky, and we can get a good amount of drug to that area without much issue. But as you move further away from the core, the BBB starts to close-up and looks more like the normal barrier you’d find in someone without a brain tumour, which blocks most therapies from entry.

This becomes a problem because while we can target the tumour core effectively, the microscopic tumour cells that are hiding further out, beyond the core, are protected by this intact BBB. They’re essentially “hiding” in these areas, and over time – 6 to 12 months after we’ve completed treatment – they can grow easily and rapidly, as well as become resistant to the therapy we previously used. The tumour cells might have had limited exposure to the treatment, but not enough to kill them. Instead, they adapt and build resistance.

Our current research is focused on finding ways to transiently open the BBB in these distant areas where the tumour cells are hiding, allowing us to get therapies into regions that are usually protected by the normal BBB. This would give us a better chance of targeting those resistant tumour cells before they can grow back.

Are there any novel approaches to drug delivery that you find particularly promising?

Am I biased to say our research?

Joking aside, I’m particularly interested to see how different people approach the same problem. As I mentioned our lab is focused on the BBB itself. Some other labs are exploring nanoparticles to cross the BBB and delivering drugs that way. I’m also fascinated by techniques like focused ultrasound, which uses sonic waves to open the BBB in specific brain regions.

I feel so passionate about the new approaches coming into the field, all looking at the same question but in so many ways. So not just one approach, but the fact that multiple smart people are thinking about this one problem.

How do you think paediatric and adult oncology researchers should work together?

My research focuses on children and young adults, and we often think of adults as being 18 and over. But it’s not uncommon for someone over 18 to develop a brain tumour that’s more typical in a child under 18. So, one of the big questions is: Do we treat a 25-year-old like they’re 5, or as an adult?

What we’ve seen is that treating a 25-year-old like a 5-year-old often leads to better outcomes. They respond better to the treatment, and their overall survival is longer. So, it’s about rethinking how we approach treatment based on the biology of the tumour, not just the age of the patient.

That’s why it’s important for adult and paediatric neuro-oncologists to communicate well, especially when dealing with patients under 39 years old. This adolescent and young adult group often falls into a grey area where it’s not always clear how best to treat them, or how much treatment they can handle. So, strong collaboration and engagement between both sides is crucial for this age group.

In line with different researchers taking different approaches to the same problem, how important do you think cross-disciplinary approaches are in advancing paediatric cancer research?

Cross-disciplinary collaboration is crucial. Engineers, physicists, and mathematicians bring fresh perspectives to the field of cancer research, which is essential because cancer is such a complex and adaptive disease. For instance, engineers working on nanoparticles and physicists studying the stiffness of tumour microenvironments are making significant contributions that complement traditional biological approaches. This collective intelligence is what will ultimately help us outsmart cancer.

Finally, what do you think will drive progress in the understanding of tumours in children and young people?

The most important driver of progress will be communication and collaboration. Communication is king, so going to conferences like Black in Cancer and networking with people both in the sciences and arts – it’s through these interactions that new, innovative approaches can emerge, and we can continue making strides towards better treatments for childhood cancers.