Functionally defined therapeutic targets in diffuse intrinsic pontine glioma

Nat Med. 2015 Jun;21(6):555-9. doi: 10.1038/nm.3855. Epub 2015 May 4.

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzazepines / administration & dosage*
  • Brain Stem Neoplasms / drug therapy*
  • Brain Stem Neoplasms / genetics
  • Brain Stem Neoplasms / pathology
  • Disease Models, Animal
  • Drug Synergism
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Hydroxamic Acids / administration & dosage*
  • Indoles / administration & dosage*
  • Panobinostat
  • Pyrimidines / administration & dosage*
  • Sequence Analysis, RNA
  • Xenograft Model Antitumor Assays

Substances

  • Benzazepines
  • GSK-J4
  • Hydroxamic Acids
  • Indoles
  • Pyrimidines
  • Panobinostat

Associated data

  • dbGaP/PHS000900.V1.P1