期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 79, 期 7, 页码 746-753出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlaa042
关键词
INI1; Malignant rhabdoid tumor; MEK162; Pediatric brain tumor; RAS
资金
- Alex's Lemonade Stand Foundation
- Giant Food Pediatric Cancer Research Fund
- National Cancer Institute [P30CA006973]
- NCI T32 training grant [5T32CA060441]
Atypical teratoid/rhabdoid (AT/RT) tumors are the most common malignant brain tumor of infancy and have a poor prognosis. We have previously identified very high expression of LIN28A and/or LIN28B in AT/RT tumors and showed that AT/RT have corresponding increased expression of the mitogen-activated protein (MAP) kinase pathway. Binimetinib is a novel inhibitor of mitogen-activated protein kinase (MAP2K1 or MEK), and is currently in pediatric phase II clinical trials for low-grade glioma. We hypothesized that binimetinib would inhibit growth of AT/RT cells by suppressing the MAP kinase pathway. Binimetinib inhibited AT/RT growth at nanomolar concentrations. Binimetinib decreased cell proliferation and induced apoptosis in AT/RT cells and significantly reduced AT/RT tumor growth in flank xenografts. Our data suggest that MAP kinase pathway inhibition could offer a potential avenue for treating these highly aggressive tumors.
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