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 (US) |
|---|---|
| Pages (from-to) | 311-323 |
| Number of pages | 13 |
| Journal | Cancer Cell |
| Volume | 29 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 14 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cell Biology
- Cancer Research
Cite this
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 journal › Article
}
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 - http://www.scopus.com/inward/record.url?scp=84962840797&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962840797&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2016.02.011
DO - 10.1016/j.ccell.2016.02.011
M3 - Article
VL - 29
SP - 311
EP - 323
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 3
ER -