Investigations of the Expression, Activation and Functional Significance of Platelet-derived Growth Factor Receptor in Pediatric Glioblastoma
Year: 2015
Type: dissertation
Abstract: Solid tumours arising from malignant transformation of glial cells are one of the leading causes of central nervous system tumour-related death in children. Recurrence in spite of rigorous surgical and chemoradiation therapies remains a major hurdle in management of these tumours. Here, we investigate the efficacy of the second-generation receptor tyrosine kinase (RTK) inhibitor nilotinib as a therapeutic option for the management of pediatric glioblastoma. We have utilised two independent pediatric glioblastoma cell lines with either high expression of platelet-derived growth factor receptor alpha (PDGFRα) or PDGFRβ expression in in vitro assays to investigate the specific downstream effects of nilotinib treatment. We show that nilotinib inhibits ligand-dependent activation of PDGFRα and suppresses AKT signalling. Nilotinib furthermore decreases cell proliferation and colony formation, as well as in vivo growth of xenograft tumours. Our results suggest that nilotinib may be effective for management of a PDGFRα-dependent group of pediatric high-grade gliomas.
Source: TSpace (University of Toronto)
Author: Karolyn Au
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2567572939