Dr. Michelle Monje, is a pediatric neuro-oncologist at Stanford University and one of the world’s top researchers in the study of high grade-gliomas. In 2017, The ChadTough Foundation and Michael Mosier Defeat DIPG Foundation awarded a research grant to Dr. Monje for her project, “The Tumor Microtube Network in DIPG: Targeting a Possible ‘Achilles Hill’ Required to Defeat DIPG.”
Through this research, Dr. Monje discovered that deadly brain tumors integrate themselves into the brain’s electrical network and then hijack signals from healthy nerve cells to fuel their own growth. Her findings were published in Nature, and The ChadTough Defeat DIPG team had an opportunity to discuss this project with her:
Q: You recently had a study published on Nature.com. Can you tell us about that?
MM: We have, for many years in my lab, been trying to understand the way that DIPG and other pediatric high grade gliomas interact with the normal brain, particularly of abnormal cells in the developing childhood brain. One thing that we’ve learned in the past and that we’ve published, is that neural activity, the activity of the brain itself, very robustly promotes the growth of DIPG and other childhood brain tumors. One of the important mechanisms that we discovered that is responsible for this is the brain activity dependent release of a particular kind of growth factor.
This is a growth factor that under normal circumstances helps to promote brain plasticity, and this overall process might have roles in learning and memory and brain development, but the cancer is hijacking it and taking advantage. When we looked at it, this mechanism seems to be so important. If we disrupt it, DIPG really can’t grow. So we’ve been trying to understand why that’s true, and that prompted us to look at the cellular consequences of exposure to this molecule.
One of the cellular consequences was upregulation of genes in the tumor cells that enable them to form networks. In adult glioblastoma this network formation had been described as occurring and it was kind of shocking to people because a previous conception of cancer is that one cell goes bad and it divides in this mindless way while some of the different cells take on different functions in the tumor. Its homogeneity but basically it’s just continuous growth. What the paper in adult glioblastoma showed was that in fact the tumor cells were connecting with each other and forming kind of a cooperative network. What we’ve discovered is the extent to which that same kind of network formation was happening in DIPG between the tumor cells, and how that might interface with how the tumor interacts with the normal brain. The study also tries to understand if this is indeed important for DIPG growth and might represent a therapeutic target.
Q: Have you seen research trickling down to other pediatric brain cancers
yet? Have you seen it making an impact?
MM: Yes, I think actually in the work I was just describing for you, that there’s a lot of cross pollination between different kinds of high grade gliomas. I described sort of a cross pollination between adult and pediatric high grade gliomas, but some of what we’ve discovered in DIPG we have found to be equally relevant to other forms of pediatric high grade gliomas. That starts some collaborations to look for similar physiologies or pathophysiologies in ependymoma and the broad area of understanding how the normal brain cells are interacting with the cancer cells. I think this is something that all pediatric brain tumor researchers need to think about; many of them are thinking about. A lot of what we’re learning in DIPG is helping to inform that.
Q: Chad Carr and Michael Mosier were diagnosed a little over 5 years ago. What are some of the differences in treatment today versus 10 years ago?
MM: In the past 5 years, a number of laboratory studies on DIPG have identified new promising treatment for DIPG, from immunotherapy to novel drugs targeting epigenetic, metabolic and microenvironmental vulnerabilities of DIPG. Several new clinical trials based on these laboratory studies are now opening. We know more about the biology of DIPG than ever before, and soon that new knowledge may lead to effective therapy.
Q: What is the importance of private funding, such as the ChadTough Defeat DIPG grant you received for this project, in moving the field of DIPG forward?
MM: Private funding enables researchers to be more nimble and pursue new ideas more rapidly.
Q: What do you think the impact will be of this groundbreaking discovery? Will it drive changes in treatment for DIPG patients?
MM: Our new appreciation that DIPG integrates into neural circuitry opens up a whole new dimension of possible therapeutic targets that I am hopeful will make a difference in outcomes for children with this terrible brain cancer.