DNAR-13. SONIDEGIB AND GANT61 INDUCE DNA DAMAGE 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 leads to 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 patient population. dysregulation constitutive activation Sonic Hedgehog (SHH) signaling pathway accounts ~30% medulloblastomas. In addition playing role tumorigenesis, SHH known play sensitivity recurrence. We hypothesize inhibiting at Smoothened (Smo) or Gli1 will increase DNA damage, resulting cell killing following therapy. found treatment medulloblastoma with drug Sonidegib GANT61 expression respective targets Smo Gli1. Both drugs also significantly FANCD2, damage repair gene essential homologous recombination. Pretreatment resulted functionally viability self-renewal radiation. These data suggest inhibition are promising increasing medulloblastoma.