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; Marcel Kool; Stefan M. Pfister; Michael D. Taylor; Robert J. Wechsler-Reya

doi:10.1016/j.ccell.2016.02.011

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

Marcel Kool, Stefan M. Pfister, Michael D. Taylor, Robert J. Wechsler-Reya

Research output: Contribution to journal › Article › peer-review

219 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 language	English
Pages (from-to)	311-323
Number of pages	13
Journal	Cancer Cell
Volume	29
Issue number	3
DOIs	https://doi.org/10.1016/j.ccell.2016.02.011
Publication status	Published - 14 Mar 2016
Externally published	Yes

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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

@article{8479be5d27734caaac7166e7a89f1e1b,

title = "HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = mar,

day = "14",

doi = "10.1016/j.ccell.2016.02.011",

language = "English",

volume = "29",

pages = "311--323",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

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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, YJ, 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

TY - JOUR

T1 - HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma

AU - Pei, Yanxin

AU - Liu, Kun Wei

AU - Wang, Jun

AU - Garancher, Alexandra

AU - Tao, Ran

AU - Esparza, Lourdes A.

AU - Maier, Donna L.

AU - Udaka, Yoko T.

AU - Murad, Najiba

AU - Morrissy, Sorana

AU - Seker-Cin, Huriye

AU - Brabetz, Sebastian

AU - Qi, Lin

AU - Kogiso, Mari

AU - Schubert, Simone

AU - Olson, James M.

AU - Cho, Yoon Jae

AU - Li, Xiao Nan

AU - Crawford, John R.

AU - Levy, Michael L.

AU - Kool, Marcel

AU - Pfister, Stefan M.

AU - Taylor, Michael D.

AU - Wechsler-Reya, Robert J.

PY - 2016/3/14

Y1 - 2016/3/14

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84962840797

U2 - 10.1016/j.ccell.2016.02.011

DO - 10.1016/j.ccell.2016.02.011

M3 - Article

C2 - 26977882

AN - SCOPUS:84962840797

SN - 1535-6108

VL - 29

SP - 311

EP - 323

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

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

Abstract

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