Novel Drug Discovery for Glioblastoma Multiforme Using Brain Tumour Initiating Cells

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.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Neuroscience

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2013

Author dc:creator

• Nguyen, Stephanie

Advisors dc:contributor.advisor

• Weiss, Samuel
• Luchman, Artee

• Molecular
• Neuroscience
• Oncology

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/27130

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/787