Research Update: Tracking how glioblastoma evolves to outsmart treatment

Glioblastoma (GBM) remains one of the most aggressive and difficult-to-treat cancers, with most tumours returning despite surgery, radiation and chemotherapy. A major challenge in improving outcomes is understanding how these tumours adapt and evolve to evade treatment. 

Supported by a Clinician-Scientist Award from the Marathon of Hope Cancer Centres Network (MOHCCN), Dr. Ana Nikolic (University of Calgary) set out to map how GBM tumours change between initial diagnosis and recurrence. By combining advanced imaging techniques with large-scale genomic and epigenetic analyses – including data from the Network’s Gold Cohort – she was able to develop new tools to examine tumour cells and their surrounding environment in unprecedented detail. Their work has revealed that specific DNA regulatory regions can change in predictable ways as tumours recur, offering new insight into how GBM resists therapy. 

These findings are helping to lay the groundwork for more precise approaches to diagnosis and treatment. By better understanding the biological features that drive recurrence, clinicians may one day be able to identify high-risk tumours earlier and match patients to more effective, personalized therapies. 

We spoke with the Dr. Nikolic to better understand the goals, discoveries and impact of this project. 

How would you describe the original objectives of your project to a lay audience? 

Glioblastoma (GBM) is the most common malignant brain tumour in adults, and almost always returns after treatment. The objectives of my project were to use several experimental approaches to understand how patient GBM tumours change when they escape therapy. First, we used a new imaging method to look at changes in the tumour cells and their surrounding environment in primary and recurrent tumours, building a panel of markers that allow us to identify different kinds of tumour cells, and how they change in relapsed tumours. We also looked at large numbers of genome sequencing data from primary and relapsed tumours, to look for DNA changes outside of genes, in regions called regulatory elements.  

What were you able to achieve through this project? How did funding from the Marathon of Hope Cancer Centres Network help you achieve these goals? 

This project has enabled my research group to build new platforms and tools. For example, we built a new imaging panel that allows us to examine pathology samples and patient-derived tumour models from patients in much greater detail than we could before. Optimizing such tumour imaging panels and developing robust pipelines for analysis requires a lot of time and money, and funding from the MOHCCN was essential to getting this platform off the ground. We have also assembled one of the largest cohorts of combined epigenetics and genetics data on GBM, incorporating multiple external cohorts, enabling us to find even uncommon links between gene regulation and tumour genetics. Our genetic analyses showed that certain DNA regions, which some GBM tumours carry in hundreds of copies, change in predictable ways when tumours recur, potentially helping them evade treatment. 

How are these findings helping to advance precision medicine for cancer? What potential impact could they have on patients? 

Understanding the way that tumours escape treatment is critical for developing the next generation of anti-cancer drugs. Multimodal imaging panels like the one my lab has developed could one day become part of routine neuropathology workflows. Being able to understand the tumours and their surrounding cells at the time of surgery will help us to identify patients whose tumours will behave poorly, and help us to match patients to therapies. 

How has funding from the Network helped advance your career as a clinician-scientist? Has becoming part of the Network helped open new opportunities? 

Funding from the Network has been essential to my career as a clinician-scientist. It has helped me establish my lab, build our laboratory’s expertise in multiple areas, and get multiple projects off the ground. The tools and datasets we have established as part of this project remain extremely valuable, and will help us as we keep working to better understand and treat GBM tumours. Being part of the MOHCCN and PR2C has helped me connect with other early career scientists and clinician scientists across Canada, and the high-quality genomics data from Gold Cohort played a key part in my project.