Rhiannon Barrow was awarded a Brain Research UK PhD studentship in 2018 to enable her to pursue research into the brain tumour glioblastoma.
She worked with supervisor Dr Lucy Stead to investigate the apparent immortality of treatment-resistant glioblastoma cells.
Following successful completion of an ambitious programme of work, Rhiannon was awarded her PhD from the University of Leeds in January 2023.
Glioblastoma (GBM) is the most common primary brain cancer in adults, with around 2,500 cases diagnosed every year in the UK.
It is a grade 4 brain tumour, meaning that it grows and spreads quickly and is difficult to treat. The infiltrative nature of the tumour makes it impossible to remove surgically in its entirety, as it has finger-like tentacles that wrap around vital brain structures.
For those affected, the prognosis is bleak. Despite aggressive treatment – including surgery, radiotherapy and chemotherapy - only a quarter of patients survive more than a year from diagnosis.
Whilst a number of drugs have been designed to target the specific molecular features of GBM, all have so far failed to prolong survival. This is likely because of inherently treatment-resistant cells that evade therapy, continuing to proliferate to form a recurrent tumour.
Working with supervisor Dr Lucy Stead, Rhiannon investigated genetic differences between pairs of initial and recurrent tumours from the same patients. They identified a gene - SLC6A6 - that is consistently present in higher amounts in recurrent tumours, indicating that it might be involved in treatment resistance and tumour recurrence.
SLC6A6 encodes for a protein called TauT. To investigate the importance of SLC6A6 and TauT on treatment resistance, Rhiannon used patient GBM samples to grow miniature tumours known as spheroids, and inhibited the activity of TauT in these spheroids to see if this affected the response to chemoradiotherapy.
She developed an automated technique that enabled her to image almost 100 spheroids every two minutes; this was published as a method and, as such, is now available to other scientists, facilitating high-throughput investigation into the effect of different treatments on GBM.
Rhiannon demonstrated that inhibiting TauT altered treatment response in different directions in different GBM samples, with the response appearing to correlate with levels of a neurotransmitter known as GABA. She also found that different GBM samples responded to treatment by changing expression of their genes in different ways, indicating that there may be different treatment resistance mechanisms. This suggests that stratifying treatment based on the response subtype could be beneficial, and highlights the importance of a personalised approach to treatment. This opens up a number of important avenues of research, which are being progressed within Dr Stead’s group.
Glioblastoma is one of the most devastating forms of cancer. It is resistant to current forms of therapy and the prognosis remains dismal for those affected.
Rhiannon’s research has helped unravel the mechanisms underpinning treatment resistance so that we can find new ways to attack the tumour. It has highlighted the importance of a personalised approach to treatment and opened up some new avenues of research. We hope that the ultimate impact for patients will be more effective treatment and prolonged survival.
Equally important, through this PhD studentship, we have helped nurture the development of a talented young researcher. Rhiannon was awarded her PhD from the University of Leeds in January 2023, and is now taking a break from lab research to pursue a career as a data analyst.
Barrow,R, Wilkinson, JN, He, Y, Callaghan, M, Brüning-Richardson, A, Dunning, M, & Stead, LF. SpheroidAnalyseR-an online platform for analyzing data from 3D spheroids or organoids grown in 96-well plates. Journal of biological methods, 9(4), (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040300/
Tanner, G, Barrow, R, Ajaib, S et al. IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy. Genome Biol 25, 45 (2024). https://doi.org/10.1186/s13059-024-03172-3
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