It is predicted that in the UK over one thousand people will be diagnosed with cancer every day this year 1. Those unlucky enough to develop the most common form of brain cancer (Glioblastoma) will typically only survive 12 to 15 months 2. But what if you could kill the cancer with your brain? Unfortunately, I don’t mean cancer-fighting psychic powers (I know, the picture of Jean Grey is misleading… it was a cruel hook!). Instead, I’m referring to a new use for neural stem cells (NSC), to do the job of tracking and killing down cancerous cells for us. Believe it or not there are scientists working on such an intervention, and a new paper 3 published last month in Nature Communications describes an exciting advancement that could help bring this strange therapy to a cancer clinic near you.
NSCs are unusual for various reasons, but of particular interest here, they’re able to migrate through the brain towards tumorous cancer cells. By engineering these cells to also secret anti-cancer molecules, they become natural cancer hunters capable of both finding and killing tumorous cells. This has been demonstrated as an effective therapy in various pre-clinical models, but the difficulty has been finding a good cell source to move this concept into clinics. Ideally we need something autologous (to stop our immune systems killing the NSC) and readily available. Unfortunately, the naturally occurring NSCs we all have exist deep within our brains (making them hard to obtain), and haven’t been genetically modified to secrete those important anticancer molecules (they’re not natural cancer killers).
Previously, scientists have wondered if we could make our own NSCs for this treatment by using induced Pluripotent Stem cells (iPSC). To learn more about iPSCs watch this short video:
iPSCs seem like they would be ideal because they are easy to get hold of (we can grow them from a skin sample), genetic modification can be made during the initial generation process, and they can be autologous to the patient. However, labs that have transplanted NSCs grown from iPSCs into the brain frequently report that iPSCs also have a really REALLY frustrating tendency to become cancerous tumour cells… and you’re not going to fix brain cancer by sticking more in there!
So what’s different about this paper? Simple; they used transdifferentiation. What the heck is transdifferentiation? I’m glad you asked. It’s a method similar to iPSC generation, except that instead of reprogramming cells to a pluripotent state, you reprogram them directly into the cell type you want. In this case they took fibroblasts (skin cells) and transdifferentiated them into NSCs, and named these new cells induced neural stem cells (iNSC). Crucially, these iNSC don’t seem to have the same tendency to become cancerous, yet they retain all those benefits of iPSCs outlined above! The researchers found that by injecting these iNSC into mice with glioblastomas, their survival increased between 160%-220%!
The iNSCs aren’t ready for clinics yet. For instance, one problem the paper outlines is that their iNSCs need a structure to help target the right parts of the brain, because otherwise they wander off before they’ve killed all the cancer. But, because these cells work so well, the scientists are confident the work only needs refinements*, so maybe one day in the not too distant future we can expect to be killing brain cancers with our brains!**
- Statistics Fact Sheet, 2015, Macmillan Cancer Support
- World Cancer Report, 2014, World Health Organisation
- Bagó, J.R., Alfonso-Pecchio, A., Okolie, O., Dumitru, R., Rinkenbaugh, A., Baldwin, A.S., Miller, C.R., Magness, S.T. and Hingtgen, S.D. (2016) Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. Nature communications, 7.
*Of course, ‘refinements’ usually translates to another decade or two of work.
**Disclaimer: This statement is technically true, though your ‘cancer killing brain’ might actually be skin cells that have been turned into genetically modified brain cells. 😉 TECHNICALITY!