MDB-36. SONIDEGIB, GANT61, AND VELIPARIB TREATMENT BOTH ALONE AND IN COMBINATION INCREASES RADIATION SENSITIVITY IN PEDIATRIC SONIC HEDGEHOG MEDULLOBLASTOMA

Abstract Medulloblastoma is the most common malignant brain tumor in children, accounting for 20-25% of all pediatric tumors. The current standard care includes both craniospinal and focal radiation therapy which lead to negative long term consequences population such as bone tissue hypoplasia, decreased neurocognitive functioning, well an increased risk secondary induced cancers. Thus, there a need novel approaches that can effectively target kill cells while minimizing toxicity healthy tissue. Here, we investigate new approach relying on two classes therapeutic agents, Sonic Hedgehog (SHH) inhibitors Poly (ADP-ribose) Polymerase (PARP) inhibitors. dysregulation constitutive activation SHH signaling pathway accounts ~30% medulloblastomas. In addition playing role tumorigenesis, known play sensitivity various cancer types. PARP1 key DNA damage repair, it has previously been shown affect cancers including high grade glioma, medulloblastoma, ependymoma. We hypothesize inhibiting at Smoothened (Smo) or Gli1 will enhance medulloblastoma cell killing following therapy. found vitro treatment with Sonidegib, GANT61, Veliparib alone without was sufficient decrease viability self-renewal. When followed by radiation, pre-treatment Veliparib, combination, resulted further These data suggest inhibition Smo, Gli1, combination promising strategy increasing medulloblastoma.