Project Summary Medulloblastoma (MB) is the most malignant pediatric brain tumor. Current treatments for MB patients include surgery, radiotherapy and chemotherapy but unfortunately, many patients remain incurable or suffer significant neurological, intellectual and physical disabilities. Therefore, novel therapeutic approaches are urgently needed. The integrin family of cell adhesion receptors contributes to multiple cellular functions crucial to tumor initiation, progression and metastasis. However, it remains unknown whether targeting integrin signaling has therapeutic benefits in MB. We recently found expression of 1- integrin (ITGB1) is overexpressed in MB tissues. Moreover, GLPG-0187, a broad- spectrum integrin receptor antagonist, significantly inhibits MB cell growth in vitro and in vivo. Based on our novel results, we hypothesize that targeting integrin signaling by GLPG-0187 may lead to novel therapies for MB patients. To test this, we propose to determine the action mechanisms of GLPG-0187’s in MB, and to determine whether GLPG-0187 inhibits tumor growth in MB preclinical animal models. The anticipated results of these studies are functional and mechanistic evaluations for the efficacy of GLPG-0187 in MB, which will accelerate the development of potential therapeutics into clinic for MB.