Dr Claudia Barros, Plymouth University
Understanding the cellular changes leading to the formation of the brain tumour glioblastoma
Dr Claudia Barros was awarded a Brain Research UK project grant in September 2017 for her study of the mechanisms underlying formation of the brain tumour glioblastoma.
Glioblastoma is the most common primary malignant brain tumour in adults. Its impact is devastating - there is no cure and most patients die within a year of diagnosis.
Dr Barros will be studying the cancer stem cells within glioblastoma. These are thought to drive tumour recurrence after treatment. Little is known about the properties of these stem cells but they may hold the key to the development of new and more effective treatments for glioblastoma.
Following rigorous assessment as part of our competitive project grant round, this project was selected for funding because the members of our Scientific Advisory Panel felt that it would make an important contribution to knowledge in an important area, with high unmet need. Based on excellent preliminary data, the Panel agreed that the work was compelling and likely to succeed.
Around 2,600 people are diagnosed with glioblastoma every year in the UK. Only 20 per cent survive for more than a year, and only three per cent survive more than three years.
Glioblastoma is a grade 4 brain tumour, meaning that it grows and spreads quickly.
It is difficult to remove surgically because it infiltrates the brain, with finger-like tentacles that often wrap around vital brain structures. Following surgery to remove the bulk of the tumour, radiation and chemotherapy are used in an effort to slow the growth of remaining tumour.
Targeting brain cancer stem cells in glioblastoma
Cancer stem cells are a group of cells within a tumour that are particularly resistant to therapy. Even if most other tumour cells are eradicated, the cancer stem cells can remain and cause the tumour to re-grow.
Understanding the properties of these cancer stem cells – and finding a way to destroy them – could therefore hold the key to the more effective treatment of tumours. Yet, despite ongoing research efforts from teams around the world, knowledge in this area remains very limited.
Working in collaboration with colleagues from Derriford Hospital in Plymouth and the Medical Research Council Centre for Regenerative Medicine in Edinburgh, Dr Barros is deciphering the mechanisms responsible for the formation and development of cancer stem cells in glioblastoma.
The project builds on previous work in which they used a sophisticated system to model human glioblastoma cancer stem cell and tumour development using the fruit fly Drosophila.
This model enables them to visualise the cancer stem cells at the time they originate inside the intact brain and identify early cellular and molecular changes. They have been able to identify molecules that are differently expressed in the cancer stem cells and normal brain cells.
More than 70 per cent of the molecules identified in this preliminary work have matching molecules in humans. The team will now explore the properties of these molecules in glioblastoma stem cells from human patients, evaluating properties such as cell proliferation, cell death and ability to (re)form cell masses.
Dr Barros is using a highly original approach to address important questions concerning how malignant brain tumours form and why they frequently recur after treatment. The limited knowledge in this area has so far hampered the development of effective targeted therapies.
The new factors and mechanisms that Dr Barros hopes to reveal have the potential to become new targets for the treatment of these deadly brain tumours, offering hope to those affected by this devastating brain tumour in the future.
“Glioblastoma is a fatal cancer, and therefore basic research helping to understand the underlying mechanisms is highly appreciated and is indeed crucial for further therapy development. The proposed work is therefore highly important and original.” External reviewer.
Related research projects
Research into brain tumours is one of our current priority research areas, reflecting the large unmet need in this area. Our aim is to fund projects that will help us to understand the causes and underlying mechanisms of brain tumours, and help us to diagnose and treat them more effectively.
Other projects currently funded under this theme include:
- Professor Chris Jones, The Institute of Cancer Research: The search for new treatments for the childhood brainstem tumour DIPG
- Rhiannon Barrow, University of Leeds: Overcoming treatment resistance glioblastoma (PhD studentship)
- Richard Baugh, University of Oxford: Targeted immunotherapy of glioblastoma (PhD studentship)