Track and trace: what causes glioblastoma recurrence?
Cancer types:
Brain cancer
Project period:
–
Research institute:
Case Western Reserve University
Award amount:
£229,362
Location:
USA
Dr. Christopher Hubert and his team in the USA aim to find the best therapy combinations to cure glioblastoma, a very aggressive type of brain tumour. By discovering the different roles of each different glioblastoma cell type, they will gain a full picture of how the cancer operates and how to best treat it.
Why is this research needed?
Glioblastoma is a deadly form of brain cancer that we currently cannot cure and that often comes back after treatment. There are two main problems that make it so hard to treat. First, the tumour is often located in parts of the brain where complete surgery is impossible. Second, the cancer cells that make up the tumor are very diverse, each with different roles, different activities, and different sensitivities to therapies.
The team hopes to discover brand new glioblastoma cures that can overcome these obstacles by better understanding the role of different cells within the tumour and how they interact.
I have always wanted to do work that is not just good science, but can make a real impact in patients’ lives. It feels good to be a part of this team and have the chance to pursue a project that could make a substantial shift in how we understand and treat brain tumours.
What is the science behind this project?
Inside glioblastoma different cancer cells live in tiny neighbourhoods constantly coordinating to help the tumour survive. The most troublesome of these are Cancer Stem Cells (CSCs), a powerful group of cells that resist therapy, keep dividing, and ultimately rebuild the tumour after it’s been treated.
Dr. Christopher Hubert and his team believe the most troublesome CSCs are the ones tucked beside blood vessels, known as perivascular CSCs. But up until now it has been very difficult to study these different cancer cell neighbourhoods. If they are removed, isolated and then studied we wouldn’t be able to see how they communicate with each other which is vital to our understanding of them.
To crack this problem, Dr. Christopher Hubert and his team have engineered a state-of-the-art tool called a Cell-Transferrable Recombinase (CTR). Think of the CTR as a tiny set of molecular scissors which one cell can use to mark another cell next to it. The team can program blood vessel cells to mark the suspected perivascular CSCs touching them, so these CSCs and all their daughter cells will glow in a different fluorescent color than the rest of the tumor.
This will give researchers a genetic and fluorescent fingerprint marking cells that descended from those original perivascular CSCs. So the team can watch where these cells move, how they spread, and how the tumour reshapes itself as it grows back following treatment. They use this knowledge to trace the exact cells responsible for GBM returning after treatment and the crucial local cellular interactions that we couldn’t study before.
What difference could this project make to patients in the future?
Thanks to Curestarter researchers this work could transform how glioblastoma is treated. This project will hopefully guide the development of treatments that directly target the true drivers of cancer relapse, bringing us closer to therapies that stop glioblastoma from coming back. This would mean better survival rates for glioblastoma patients and more precious time with their loved ones.
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