HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma

Yanxin Pei, Kun Wei Liu, Jun Wang, Alexandra Garancher, Ran Tao, Lourdes A. Esparza, Donna L. Maier, Yoko T. Udaka, Najiba Murad, Sorana Morrissy, Huriye Seker-Cin, Sebastian Brabetz, Lin Qi, Mari Kogiso, Simone Schubert, James M. Olson, Yoon Jae Cho, Xiao Nan Li, John R. Crawford, Michael L. LevyMarcel Kool, Stefan M. Pfister, Michael D. Taylor, Robert J. Wechsler-Reya

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis and would greatly benefit from more effective therapies. We used an animal model of MYC-driven MB to screen for drugs that decrease viability of tumor cells. Among the most effective compounds were histone deacetylase inhibitors (HDACIs). HDACIs potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the FOXO1 tumor suppressor gene. HDACIs also synergize with phosphatidylinositol 3-kinase inhibitors to inhibit tumor growth in vivo. These studies identify an effective combination therapy for the most aggressive form of MB.

Original languageEnglish (US)
Pages (from-to)311-323
Number of pages13
JournalCancer Cell
Volume29
Issue number3
DOIs
StatePublished - Mar 14 2016

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Pei, Y., Liu, K. W., Wang, J., Garancher, A., Tao, R., Esparza, L. A., Maier, D. L., Udaka, Y. T., Murad, N., Morrissy, S., Seker-Cin, H., Brabetz, S., Qi, L., Kogiso, M., Schubert, S., Olson, J. M., Cho, Y. J., Li, X. N., Crawford, J. R., ... Wechsler-Reya, R. J. (2016). HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma. Cancer Cell, 29(3), 311-323. https://doi.org/10.1016/j.ccell.2016.02.011