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Inhibition of MEK confers hypersensitivity to X-radiation in the context of BRAF mutation in a model of childhood astrocytoma.

Authors
  • Studebaker, Adam
  • Bondra, Kathryn
  • Seum, Star
  • Shen, Changxian
  • Phelps, Doris A
  • Chronowski, Christopher
  • Leasure, Justin
  • Smith, Paul D
  • Kurmasheva, Raushan T
  • Mo, Xiaokui
  • Fouladi, Maryam
  • Houghton, Peter J
Type
Published Article
Journal
Pediatric Blood & Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Oct 01, 2015
Volume
62
Issue
10
Pages
1768–1774
Identifiers
DOI: 10.1002/pbc.25579
PMID: 25981859
Source
Medline
Keywords
License
Unknown

Abstract

Selumetinib suppressed TORC1 signaling in the context of BRAF mutation. Selumetinib caused a rapid downregulation of FANCD2 and markedly potentiated the effect of XRT. These data suggest the possibility of potentiating the effect of XRT selectively in tumor cells by MEK inhibition in the context of mutant BRAF or maintaining tumor control at lower doses of XRT that would decrease long-term sequelae.

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