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 novel 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 (HDACI). HDACI potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the Foxo1 tumor suppressor gene. HDACI also synergize with phosphatidylinositol 3-kinase inhibitors (PI3KI) to inhibit tumor growth in vivo. These studies identify a novel and effective combination therapy for the most aggressive form of MB.

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