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

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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.

Originele taal-2	Engels
Pagina's (van-tot)	311-323
Aantal pagina's	13
Tijdschrift	Cancer Cell
Volume	29
Nummer van het tijdschrift	3
DOI's	https://doi.org/10.1016/j.ccell.2016.02.011
Status	Gepubliceerd - 14 mrt. 2016
Extern gepubliceerd	Ja

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10.1016/j.ccell.2016.02.011

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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",

number = "3",

}

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, nr. 3, blz. 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

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