A preclinical study demonstrating the efficacy of nilotinib in inhibiting the growth of pediatric high-grade glioma

Journal of Neuro-oncology
Karolyn AuGelareh Zadeh

Abstract

Solid tumors arising from malignant transformation of glial cells are one of the leading causes of central nervous system tumor-related death in children. Recurrence in spite of rigorous surgical and chemoradiation therapies remains a major hurdle in management of these tumors. Here, we investigate the efficacy of the second-generation receptor tyrosine kinase inhibitor nilotinib as a therapeutic option for the management of pediatric gliomas. We have utilized two independent pediatric high-grade glioma cell lines with either high platelet-derived growth factor receptor alpha (PDGFRα) or high PDGFRβ expression in in vitro assays to investigate the specific downstream effects of nilotinib treatment. Using in vitro cell-based assays we show that nilotinib inhibits PDGF-BB-dependent activation of PDGFRα. We further show that nilotinib is able to decrease cell proliferation and anchorage-independent growth via suppression of AKT and ERK1/2 signaling pathways. Our results suggest that nilotinib may be effective for management of a PDGFRα-dependent group of pediatric gliomas.

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Citations

Feb 25, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Magimairajan Issai VananDavid D Eisenstat
Jul 28, 2020·Pharmaceuticals·Angel Escamilla-RamírezCristina Trejo-Solís

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Methods Mentioned

BETA
surgical resection
exome sequencing
scraping
electrophoresis
ELISA
xenograft

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