Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283

William Petersen, Jingbo Liu, Liangping Yuan, Hongying Zhang, Matthew Schneiderjan, Yoon Jae Cho, Tobey J. MacDonald

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalCancer Letters
Volume354
Issue number1
DOIs
StatePublished - Nov 1 2014

Keywords

  • Aurora kinase
  • Dasatinib
  • Medulloblastoma
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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