Why is brain cancer so hard to treat?
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What is the main topic discussed in this episode?
Hey, it's Flora, and you're listening to Science Friday.
How common and devastating are brain cancers?
Brain cancers are rare but devastating. Patients face short life expectancies after diagnosis. Brain tumors are often impossible to remove completely, and the typical course of therapy, radiation and chemotherapy, doesn't always stop them from spreading. It's a daunting class of disease to study, but that didn't dissuade Dr. Michelle Mangia from trying. She's spent two decades working on understanding how brain tumors form and interact with healthy brain cells and pioneered the field of cancer neuroscience. Dr. Michelle Mangia is a professor of pediatric neuro-oncology at Stanford Medicine. Michelle, welcome to Science Friday. Thank you so much for having me. Thanks for being here. Let's go back in time.
What gaps existed in brain cancer research 20 years ago?
When you started 20 years ago, how much was understood about brain cancers?
20 years ago, there was really very little understood about the fundamental biology of brain cancers. And this wasn't for lack of effort in the field. But the approach to brain cancers was, I think, missing some really important components and also limited by... just technological abilities to study this really difficult disease and difficult to access disease. This was especially true about childhood brain cancers. When I was a medical student, I remember seeing the very first patient that I ever saw with diffuse intrinsic pontine glioma, which we now call diffuse midline glioma of the pons. This is one of the most common aggressive cancers in pediatric neuro-oncology. It is the leading cause of cancer-related death in children.
And there was just nothing known about it. And really, at the time, no way to study it. And seeing this disease unfold in the first patient that I cared for, watching this beautiful young girl who was, you know, bright light coming into the clinic with just minimal symptoms of crossed eyes and a little bit of weakness on one side, watching her lose all ability to move, to speak, to communicate and ultimately pass within six months, felt like something I just couldn't turn away from. And so I decided at the time to... really focus on these diseases and to approach them from the perspective of neurobiology. They really seem to be cancers that happened in the childhood nervous system at particular points of development at particular ages in specific locations for those ages.
And that really spoke to the idea that somehow these childhood brain cancers were diseases of brain development in childhood gone wrong. And I thought that perhaps I could approach it from that perspective.
I mean, it's interesting that it was such a black box and so devastating and that you thought, you know, I have to take this on.
Why did Dr. Michelle Monje focus on pediatric neuro-oncology?
Why did you think you might be able to make some progress?
Optimism and maybe a little bit of hubris. At the time, I was a MD-PhD student at Stanford, and I was studying neural stem and precursor cell biology. And one of the things that we had to do to study neural stem and precursor cells was to culture them from the brains either of experimental animals or in the early postmortem hours after passing from humans. So I thought that we could apply that same technique to brain cancers. One of the real problems with these diffusely infiltrative kind of intrinsic diseases like diffuse intrinsic pontine glioma is that there isn't resection tissue to study in the laboratory. You can't surgically remove these cancers. And at the time, they weren't even biopsied.
That has changed. Pediatric neurosurgeons have been trained to do very... Expertly skilled neurosurgeons have been trained to do biopsies. But at the time, there was not even biopsy tissue of diffuse midline gliomas. And so I thought maybe we could apply those techniques from neurobiology to culture, perhaps in the early postmortem period, these tumor cells.
So you'd have a model to work off of.
Exactly, because we had no way to study this in the laboratory. There was no model. This was just at the time, this is in the early 2000s to 2010s, and next generation sequencing had just come to be.
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Chapters
7 chapters
1
What is the main topic discussed in this episode?
0:02–0:06
2
How common and devastating are brain cancers?
0:06–0:54
3
What gaps existed in brain cancer research 20 years ago?
0:54–3:02
4
Why did Dr. Michelle Monje focus on pediatric neuro-oncology?
3:02–5:48
5
How did patient-derived models transform DIPG research?
5:48–7:17
6
What makes brain cancer particularly hard to treat compared to other cancers?
7:17–11:26
7
How do neurons and electrical signaling promote brain tumor growth?
11:26–17:32
Speakers
2 identifiedMore from Science Friday
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