Susanna Fletcher Greer, Chief Scientific Officer of the V Foundation, shared a post on LinkedIn:
“A V Foundation funded study reveals how one of the most aggressive childhood brain tumors protects itself from its own toxic fuel. By disabling that survival mechanism, researchers uncovered a new vulnerability that could open the door to better treatments for children with high risk medulloblastoma.
The Power of Persistence: A Breakthrough in Group 3 Medulloblastoma
International Childhood Cancer Day was February 15. It is a day that brought me back to a simple, hard truth: in pediatric cancer, progress is not abstract. Progress is time. It’s fewer long term side effects. It’s a future that feels more possible for children and their families.
A new the V Foundation funded study in Cancer Cell investigated one of the most aggressive childhood brain tumors, Group 3 medulloblastoma, and offers hopeful insight. This study shows us not just how these tumors grow, but how they survive and where they may be vulnerable. I love this paper.
For us to talk about this study, imagine a factory that produces (and needs) a lot of fuel to keep its machines running. But some of that fuel is unstable and dangerous. If too much fuel builds up, it could catch fire and damage the factory. To avoid that possibility, the staff builds secure storage tanks to lock the excess fuel away and release it only when its needed.
And that is exactly what this tumor is doing. V Foundation grantee Dr. Antony MichealRaj K. and team at UPMC analyzed nearly 400 patient tumor samples using multiple layers of biology to understand how this cancer behaves. They focused on a high-risk form of medulloblastoma driven by MYC. MYC is a powerful gene that acts like a stuck accelerator pedal, pushing cancer cells to grow fast and consume large amounts of energy. To keep up with that demand, these tumor cells make and collect large amounts of fat. But too much free fat inside a cell is toxic because it can create damaging chemical reactions.
So, the cancer protects itself by storing the fat inside tiny structures called lipid droplets. Think of these droplets as the secure storage units for the cancer cell. They serve two basic purposes: they keep excess fat from damaging the cell and they act as an energy reserve that can be used to fuel growth.
At first, Dr. Michealraj and team tried blocking the tumor’s ability to make fat. But the cancer adapted by pulling fat in from its surroundings. That’s a common theme in cancer. If we block one supply line, the tumor often finds another.
The breakthrough in this study is that Dr. Michealraj found a step the tumor could not easily bypass by focusing on an enzyme called DGAT1. This enzyme is required to package fat safely into those storage droplets.
When DGAT1 was blocked, the tumor could no longer store excess fat and the unstable fat began to cause chemical damage inside the cell…and the cancer cells died.
In animal models where tumors were growing in the brain, blocking DGAT1 slowed tumor growth and extended survival. The effect was even stronger when combined with standard chemotherapy.
Without storage, it looks like the excess fat undergoes oxidation, and the tumor’s own fuel becomes toxic when it cannot be safely stored.
Two things stand out to me:
First, this study shows how deeply we now understand these tumors. This work went beyond DNA to study proteins and metabolism, revealing important differences within what we thought was a single disease.
Second, it is a powerful example of a new strategy in cancer research. Instead of only trying to shut down growth signals, this team identified a survival systems cancer cells depend on and turned those systems against the tumor.
This is still early research. The next challenge is that current DGAT1 drugs do not yet effectively reach the brain, so more work is needed before this approach can reach patients. But the concept is very strong. The tumor survives by locking dangerous fuel away. Take away the storage system, and the cancer’s own metabolism becomes its weakness.
This is exactly the kind of progress that gives me real hope. It’s why the V Foundation leans in early in high risk, high reward research. This is not a finished therapy, but a clear and thoughtful path toward better options for children facing one of the most difficult brain cancers.”
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