Evaluation of novel drug candidates identified by omics approaches against the glioblastoma invasive margin

Mulhall, Kayley

Evaluation of novel drug candidates identified by omics approaches against the glioblastoma invasive margin

Publication Date

July 23, 2026

Creator

Mulhall, Kayley

Abstract

Glioblastoma is an aggressive and fatal brain tumour, with disease recurrence inevitable despite multimodal treatment. The tumour region associated with recurrence is known as the 'invasive margin', and further research into the molecular and cellular basis of this region is needed to prevent or delay recurrence and improve patient survival. Omics methods enable large-scale investigation of an organism's biological makeup, offering the potential to identify therapeutic targets. This project aims to identify cytotoxic therapeutics against omics-derived glioblastoma invasive margin targets, as well as identify potential protein targets in the invasive margin. In silico molecular docking identified idelalisib, domperidone, carvedilol, nilotinib, darifenacin, and lurasidone as promising therapeutic candidates against omicsderived targets. Presto Blue™ viability assays revealed six cytotoxic candidates: domperidone (IC50=~57.41 µM), carvedilol (IC50=~16.96 µM), nilotinib (IC50=~25.37 µM), darifenacin (IC50=~46.77 µM), RSM932A (IC50=~4.92 µM) and U-73122 (IC50=~14.59 µM). Cell Titre Glo assays confirmed that domperidone and carvedilol remain cytotoxic against 3D spheroids. The metabolomics-derived candidates, RSM932A and U-73122, were tested in synergy and demonstrated additive effects. These candidates also displayed minimal anti-invasive properties in a transwell invasion assay. To identify protein targets, tumour tissue samples were dissociated and subjected to 5-aminolevulinic acid-based fluorescence-activated cell sorting. Proteins from each cell population were extracted and analysed using liquid chromatography-mass spectrometry; however, the data obtained from this was unreliable. In summary, employing omics-derived targets identified potential novel therapeutic candidates against the invasive margin, thereby contributing to the expanding research field investigating this tumour region and emphasising the importance of therapeutically targeting the glioblastoma invasive margin.

Item Type

ethesis

Thesis Type

MRes

Supervisors

Rahman, Ruman