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

被引：6

作者：

Au, Karolyn ^{[1
,2
]}

Singh, Sanjay K. ^{[1
]}

Burrell, Kelly ^{[1
]}

Sabha, Nesrin ^{[1
]}

Hawkins, Cynthia ^{[1
]}

Huang, Annie ^{[1
]}

Zadeh, Gelareh ^{[1
,2
]}

机构：

[1] Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1L7, Canada

[2] Toronto Western Hosp, Div Neurosurg, Toronto, ON M5T 2S8, Canada

来源：

JOURNAL OF NEURO-ONCOLOGY | 2015年 / 122卷 / 03期

关键词：

Pediatric glioma; Nilotinib; PDGFR alpha; AKT signaling; ERK1/2; signaling; TYROSINE KINASE INHIBITOR; INTRINSIC PONTINE GLIOMAS; BCR-ABL; PDGF RECEPTOR; HISTONE H3.3; IN-VITRO; EXPRESSION; IMATINIB; AMN107; GLIOBLASTOMA;

D O I：

10.1007/s11060-015-1744-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (PDGFR alpha) or high PDGFR beta 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 PDGFR alpha. 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 PDGFR alpha-dependent group of pediatric gliomas.

引用

页码：471 / 480

页数：10

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