Novel Drug Discovery for Glioblastoma Multiforme Using Brain Tumour Initiating Cells
Date
2013-07-10
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Abstract
Glioblastoma (GBM) is the most common and aggressive adult primary brain tumour. Populations of cells with tumour initiating capacity, termed brain tumour initiating cells (BTICs), are thought to underlie the formation, growth and recurrence of GBM. As such, therapies that target this compartment may improve the otherwise poor prognosis of this disease. Here, we identified R333, a compound targeting the JAK/STAT3 pathway, as a potent inhibitor of BTIC tumourigenicity. In vitro, R333 dramatically decreased the viability and clonogenic potential of diverse BTIC lines. In vivo, systemic treatment with R348, the prodrug form of R333, was well tolerated and demonstrated favourable pharmacokinetic properties. R348 treatment was also found to lead to a significant increase in overall median survival in an orthotopic BTIC xenograft model. Altogether, these data strongly support further investigation of this compound and potentially represent the first step toward an effective molecularly targeted therapeutic for GBM.
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Keywords
Molecular, Neuroscience, Oncology
Citation
Nguyen, S. (2013). Novel Drug Discovery for Glioblastoma Multiforme Using Brain Tumour Initiating Cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27130