Tracking the spread of metastatic medulloblastoma to identify key drivers of disease progression and therapeutic vulnerabilities

Medulloblastoma, a type of childhood brain cancer, becomes much harder to treat when it spreads (metastasises) to other parts of the brain and spine. We believe that only certain tumour cells have the ability to spread, and these cells have unique characteristics that make them more aggressive.

Using novel mouse models which mirror the human disease of metastatic medulloblastoma, advanced barcoded tracking technologies and computational modelling, we aim to identify these specific cells and understand what makes them different from the ones that remain in the original tumour. By uncovering the key drivers of metastasis, we hope to find new ways to develop targeted treatments that can stop the cancer from spreading.

This research addresses a critical gap in our understanding of how medulloblastoma, a fast-growing and often aggressive brain cancer that primarily affects children, spreads to other parts of the brain and spine (a process called metastasis). Although current therapies can initially shrink or remove the primary tumour, many children present with metastatic disease at diagnosis and/or experience relapse, and the cancer that returns is often more aggressive and much harder to treat.

One of the biggest challenges is that medulloblastoma is not made up of one single type of cancer cell. Instead, it’s a complex mixture of different “clones” or groups of cells, each with their own unique characteristics. Some of these clones are more likely to survive treatment or spread to other parts of the body, but we don’t yet know why. Existing studies have mainly looked backwards at tumour samples after treatment has failed, which limits our ability to understand how these dangerous clones evolve and spread in real time.

Our project aims to fill this knowledge gap by using cutting-edge technology to track individual tumour cells over time, essentially creating a “family tree” of cancer cell evolution. By tagging each cell with a unique DNA barcode and following their behavior before and after treatment, we can determine which clones are the most dangerous, how they resist therapy, and what makes them capable of spreading.

This research is urgently needed because:
– Current treatments aren’t enough to prevent relapse or cure metastatic disease.
– Children who relapse often have poor outcomes, and the long-term side effects of aggressive treatment can be devastating.
– We lack the tools to historically predict metastases, especially in aggressive forms like Group 3 medulloblastoma.

By uncovering the biological “rules” that drive tumour evolution and spread, this project will pave the way for new, more precise therapies that target the most harmful clones early, before they have a chance to cause relapse. Funding this research is a vital step toward improving survival and quality of life for children with this devastating disease