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. Levy & 4 others Marcel Kool, Stefan M. Pfister, Michael D. Taylor, Robert J. Wechsler-Reya

Research output: Contribution to journalArticle

63 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Medulloblastoma
Phosphatidylinositol 3-Kinases
Histone Deacetylase Inhibitors
Growth
Phosphatidylinositol 3-Kinase
Therapeutics
Tumor Suppressor Genes
Brain Neoplasms
Survivors
Neoplasms
Cell Survival
Animal Models
Pediatrics
Survival
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Pei, Y., Liu, K. W., Wang, J., Garancher, A., Tao, R., Esparza, L. A., ... 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

HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma. / Pei, Yanxin; Liu, Kun Wei; Wang, Jun; Garancher, Alexandra; Tao, Ran; Esparza, Lourdes A.; Maier, Donna L.; Udaka, Yoko T.; Murad, Najiba; Morrissy, Sorana; Seker-Cin, Huriye; Brabetz, Sebastian; Qi, Lin; Kogiso, Mari; Schubert, Simone; Olson, James M.; Cho, Yoon-Jae; Li, Xiao Nan; Crawford, John R.; Levy, Michael L.; Kool, Marcel; Pfister, Stefan M.; Taylor, Michael D.; Wechsler-Reya, Robert J.

In: Cancer Cell, Vol. 29, No. 3, 14.03.2016, p. 311-323.

Research output: Contribution to journalArticle

Pei, Y, Liu, KW, Wang, J, Garancher, A, Tao, R, Esparza, LA, Maier, DL, Udaka, YT, Murad, N, Morrissy, S, Seker-Cin, H, Brabetz, S, Qi, L, Kogiso, M, Schubert, S, Olson, JM, Cho, Y-J, Li, XN, Crawford, JR, Levy, ML, Kool, M, Pfister, SM, Taylor, MD & Wechsler-Reya, RJ 2016, 'HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma', Cancer Cell, vol. 29, no. 3, pp. 311-323. https://doi.org/10.1016/j.ccell.2016.02.011
Pei Y, Liu KW, Wang J, Garancher A, Tao R, Esparza LA et al. HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma. Cancer Cell. 2016 Mar 14;29(3):311-323. https://doi.org/10.1016/j.ccell.2016.02.011
Pei, Yanxin ; Liu, Kun Wei ; Wang, Jun ; Garancher, Alexandra ; Tao, Ran ; Esparza, Lourdes A. ; Maier, Donna L. ; Udaka, Yoko T. ; Murad, Najiba ; Morrissy, Sorana ; Seker-Cin, Huriye ; Brabetz, Sebastian ; Qi, Lin ; Kogiso, Mari ; Schubert, Simone ; Olson, James M. ; Cho, Yoon-Jae ; Li, Xiao Nan ; Crawford, John R. ; Levy, Michael L. ; Kool, Marcel ; Pfister, Stefan M. ; Taylor, Michael D. ; Wechsler-Reya, Robert J. / HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma. In: Cancer Cell. 2016 ; Vol. 29, No. 3. pp. 311-323.
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