Investigating anti-tumour effects and associated metabolomic impacts of repurposed therapeutics for glioblastoma
Publication Date
March 15, 2026
Creator
Abstract
Isocitrate dehydrogenase wild-type glioblastoma (GBM) is an aggressive brain tumour, requiring effective therapies against its progression. Drug repurposing offers a promising and efficient approach to accelerate drug development of GBM. In previous work, Afuresertib, Taxifolin and Caledonine were repurposed as candidates for GBM treatment.
First, their anti-tumour effects and associated metabolic impacts were investigated using primary GBM cells. Of these, Afuresertib was identified as the greatest potential, exhibiting strong anti-tumour activity in vitro and having a clinically favourable safety profile. Metabolomics analysis revealed that Afuresertib and Caledonine could disrupt amino acid metabolism, energy metabolism, and glycerophospholipid metabolism to exert anti-tumour function, while Taxifolin could affect histidine metabolism and nicotinate and nicotinamide metabolism, leading to tumour cell death. Additionally, metabolic heterogeneity was observed between cells derived from the tumour core and their counterparts from the invasive margin, with glycerophospholipid metabolism as a significant differentiating factor.
Next, to investigate the metabolic signatures associated with GBM invasion, single-cell metabolomics was conducted using 3D OrbiSIMS and AP-MALDI-MS. Glycerophospholipid metabolism was identified by both independent methods as a significantly changed pathway between invaded and non-invaded cells.
Finally, a capillary-flow LC-MS-based metabolite profiling method (1 μL/min) was developed as a complementary approach to study the metabolic mechanisms underlying GBM invasion, capable of profiling metabolites from as few as 5,000 GIN31 cells. Glycerophospholipid metabolism was again identified as significant, further supporting its involvement in GBM invasion. Additional pathways suggested that invaded cells could reprogramme energy metabolism and remodel extracellular matrix, whereas non-invaded cells tend to maintain cellular homeostasis.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Pharmacy (UK)
eprints ID
83093
UoN Repository URI
Except where otherwise noted, this item's license is described as
File(s)![Thumbnail Image]()
Name
PhD_Thesis_Rui_Chen_Final_submission_20260105.pdf
Type
Full-text
Description
Examined
Size
47.49 MB
Format
Adobe PDF
Checksum (MD5)
9949a9994cc58ab0a689c9ee77deb9d9