Issues with treating brain cancers through the blood-brain barrier

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Published: 11 May 2018
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Dr Tim Phoenix - Cincinnati Children’s Hospital Medical Center, Cincinnati, USA

Dr Phoenix talks to ecancer at the Cancer Research UK Brain Tumour Conference 2018 in London about the blood-brain barrier and the challenges faced when treating brain tumours.

He goes on to discuss how the blood-brain barrier is an obstacle to get drugs into the target tumour site to treat.

It’s talking about the blood-brain barrier within brain tumours and some of the developmental pathways that actually control blood-brain barrier formation and how some of these pathways are modulated in different brain tumour entities.
The blood-brain barrier is this physical barrier that doesn’t allow certain compounds into the brain. It’s normally very good, so it protects your cells in your brain, allows you to function properly. Then when you have a brain tumour it becomes an obstacle to actually get drugs into the tumour to properly treat it. What we’ve noticed over the last few years is we’ve expanded on our understanding of differences in brain tumours, so instead of just having a group or two groups, now we’ve got lots of different groups. These differences are really focussed on cell intrinsic, so really tumour cell, biology but, of course, the tumour cells talk to blood vessels which have this barrier. Sometimes it breaks them down, sometimes it doesn’t  and what this was talking about was a discovery that we made whilst I was a post-doctoral Fellow with Richard Gilbertson where this Wnt tumour which responds very well to current treatment, which includes surgery, radiation and chemotherapies. So these tumours are fairly unique because they secrete these molecules that actually block normal blood-brain barrier formation. So the signal that normally instructs the vessels to turn on this barrier are essentially turned off within this brain tumour because of just what happens within the tumour. So understanding these little nuances in terms of not every tumour is the same, and we know this within tumour cells, then we need to start expanding on that in terms of the tumour microenvironment which includes blood vessels.

One of the real impediments of treatment is getting it into these brain tumours, so really understanding what are the signals that regulate this barrier and how we can use that understanding to manipulate it, whether it’s directly manipulating those signalling pathways or other ones that are associated with it. How can we use this understanding to improve drug penetration into these tumours?

What does this mean for patients?

You’re getting this treatment, whether it’s chemotherapy or a novel compound, and a lot of these compounds, especially these small molecules, just don’t get into the brain normally. If you’re having a tumour treated, maybe it’s been resected and you still have a residual tumour, and a lot of adult tumours are very aggressive and they’ll spread through the brain. In these areas there’s still an intact barrier so you might be getting this drug and it might not even be getting to the tumour. So this is really understanding how we can get… We’re trying to treat this tumour, this cell, how can we get the drugs there better?