Nature Communications (Oct 2017)

Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL

  • Georg Karpel-Massler,
  • Chiaki Tsuge Ishida,
  • Elena Bianchetti,
  • Yiru Zhang,
  • Chang Shu,
  • Takashi Tsujiuchi,
  • Matei A. Banu,
  • Franklin Garcia,
  • Kevin A. Roth,
  • Jeffrey N. Bruce,
  • Peter Canoll,
  • Markus D. Siegelin

DOI
https://doi.org/10.1038/s41467-017-00984-9
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 14

Abstract

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Glioblastoma (GBM) cells are often characterized by the presence of the IDH1 R132H mutation and high expression of anti-apoptotic proteins. Here, the authors show that the inhibition of Bcl-xL is synthetically lethal in IDH1-mutated GBM models and that this effect is mediated by the oncometabolite, 2-HG, which reduces Mcl-1 protein levels.