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Open Access 01-05-2015 | Laboratory Investigation

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

Authors: Karolyn Au, Sanjay K. Singh, Kelly Burrell, Nesrin Sabha, Cynthia Hawkins, Annie Huang, Gelareh Zadeh

Published in: Journal of Neuro-Oncology | Issue 3/2015

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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Title: A preclinical study demonstrating the efficacy of nilotinib in inhibiting the growth of pediatric high-grade glioma
Authors: Karolyn Au
Sanjay K. Singh
Kelly Burrell
Nesrin Sabha
Cynthia Hawkins
Annie Huang
Gelareh Zadeh
Publication date: 01-05-2015
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 3/2015
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-015-1744-y

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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