STEM-26. ASTROCYTIC SOX2+ CELLS RELAY IN NON-CANONICAL GLI SIGNALING TO FACILITATE MEDULLOBLASTOMA RELAPSE

Abstract Medulloblastoma is the most common malignant pediatric brain tumor. Despite fair efficacy of current treatment approaches, 30 % patients with medulloblastoma relapse. Cells expressing stemness biomarker SRY (sex determining region Y)-box 2 (SOX2) are known to play key roles in sustaining growth, providing chemo-resistance, and driving tumor It therefore critical elucidate underlying mechanisms that propagate these cells ensure therapies target them. Single cell sequencing analyses revealed existence a subset astrocyte-like SOX2+ biomarkers indicative SHH signaling activation. Intriguingly, such were not affected by upstream inhibitor vismodegib. Using enriched cultures, we observed SOX2 only express effectors, but require GLI proliferate, activated non-canonical MYC dependent manner. Importantly, vivo inhibition downstream SMO depleted vismodegib resistant pool, while reduced ability residual tissues engraft vivo. Our data show medulloblastoma, rely on propagate, emphasizes importance using deplete prevent recurrence.