Deploying Kinase Inhibitors to Study Pediatric Gliomas

Benjamin T. Himes, Liang Zhang, David J. Daniels

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Pediatric midline gliomas are a uniformly fatal disease for which there is no cure. The location of these tumors makes surgical resection impossible, and so novel therapies are urgently needed to improve outcomes. The biology of these tumors is increasingly understood, with the histone H3K27M mutation playing a critical role in the pathogenesis of these tumors. Efforts to inhibit the growth of these tumors have also focused on inhibiting the Aurora kinase and Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in order to disrupt tumor proliferation. A number of small molecule inhibitors of these kinases have shown promise in early studies. Screening and preclinical assessment of such inhibitors requires a functional assay to assess the degree of kinase inhibition. We detail here a luciferase-based reporter assay for STAT3 transcriptional activity that we have employed frequently in order to assess the efficacy of kinase inhibitors in pediatric gliomas. The assay we describe is specific to STAT3, but the overall methodology is generalizable to other downstream targets of the kinase of interest.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages167-173
Number of pages7
DOIs
StatePublished - 2022
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume2415
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • DIPG
  • H3K27M
  • Kinase inhibitors
  • Luciferase assay
  • Pediatric midline glioma
  • STAT3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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