Jun 14, 2016

As the most common and aggressive cancerous brain tumour in adults, glioblastoma is lethal due to its resistance to all currently available treatments. Now, a University of Toronto professor has made a key discovery: glioblastoma seems to like the common neurotransmitter dopamine.

The discovery, by Professor Peter Dirks, of the Division of Neurosurgery and his team at The Hospital for Sick Children, opens new areas of research into treatments for the deadly disease – particularly involving ordinary brain chemicals better known for their role in neurodegenerative conditions like Parkinson’s disease. 

Scientists have long understood that when the brain lacks sufficient amounts of dopamine, Parkinson’s disease will occur. In the new study, the team identified chemicals that block dopamine function in glioblastoma tumours in the lab, essentially making glioblastoma stem cells (the cells that drive tumour formation) undergo a rapid neurodegenerative process. But instead of causing Parkinson’s, this process degraded or killed the gliobastoma stem cells. The paper is published in the June 13 online edition of Cancer Cell.

Dirks, a senior scientist at SickKids, spoke to writer Heidi Singer about his discovery.

This is fascinating research. Could it open up other new avenues into the connection between brain chemistry and brain cancer?

Thank you, and, we think this work could possibly open up new avenues.  Our study involved an initial screen with many brain neurochemical modifiers.  We found that signals involving dopamine, serotonin and other areas of the parasympathetic nervous system also affected glioblastoma cell growth.  We are pursuing some of these in further research in the lab.

Why do you think brain chemistry has been an underexplored research area for glioblastoma?

I think we need to look harder at normal brain development and function to get clues about what affects brain tumor cells.  These tumors arise from normal cells after all, and despite many genetic mutations, they still (perhaps surprisingly) retain many of the same processes for survival and growth.  I believe we need more research that looks at brain tumors through a lens of neurobiology.  Not many neurobiologists study brain cancer and vice versa, and this kind of work perhaps falls through a crack as a consequence.

Scientists have noticed that the dopamine-depleted (such as people with Parkinson’s) seem to have fewer glioblastomas. Does it follow that people with higher levels of dopamine could be at greater risk for brain tumors? 

We are just scratching the surface of this biology, so the answer is we don’t know, but I doubt that too much dopamine causes a tumor.  Our data does not say anything about the emergence of tumors with low or high dopamine —  it just says that when you have a glioblastoma, that dopamine signalling plays some role in cell survival.  More research is needed!

It’s exciting to think that drugs already on the market could be put to use right away for patients with glioblastomas. How would this work, and how soon can this start?

There are first important safety concerns as many of these agents could affect mood and behaviour, and we don’t know about the long-term use.  However, some similar compounds have been tried in people so there is some experience, but we really need more information and further study before they might be used for patients.  The goal would be to specifically alter dopamine signalling that is used by the tumor, for example, through the DRD4 receptor, but not to affect other essential dopamine-medicated brain processes.  This goal demands more clinically focused research.

We seem to be finding that conditions like schizophrenia, autism, dementia and even ordinary depression have more in common with each other than we ever thought, because they share common pathways. Would you now add brain cancer to that list? 

That’s a provocative statement.  I think all we can say right now is that brain tumors, like normal brain cells, use some of these pathways also for cell survival.

What inspired your research into glioblastomas?

We are surprised and excited by our findings and the potential clinical application.  As a neurosurgeon, I’m continually inspired by my patients.  We need to do so much better for them. Hopefully, this recent work opens some new doors and will inspire additional research so we can bring better treatments or treatment combinations to the clinic. 

Article courtesy of Faculty of Medicine, University of Toronto