MEK inhibition suppresses growth of atypical teratoid/ rhabdoid tumors

Shubin Shahab, Jeffrey Rubens, Harpreet Kaur, Heather Sweeney, Charles G. Eberhart, Eric H. Raabe

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)746-753
Number of pages8
JournalJournal of neuropathology and experimental neurology
Volume79
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • INI1
  • MEK162
  • Malignant rhabdoid tumor
  • Pediatric brain tumor
  • RAS

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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