Medulloblastoma　is　a　highly　malignant　childhood　brain　tumor　and　is　often　characterized　by　alterations　in　cell　cycle　regulatory　pathways　and　genes.　Using　FDA-approved　arsenic　trioxide　(ATO)　treated　ND2-SmoAl　mouse　model,　we　present　an　integrated　imaging　and　systems　biology　approach　to　assess　tumor　responses　to　ATO　and　to　uncover　the　complexity　of　therapeutic　molecular　biology.　Kaplan-Meier　survival　and　MRI　tumor　growth　analyses　established　the　effectiveness　of　ATO　treatment.　Differential　analysis　of　protein　data　identified　biologically　plausible　gene　markers.　Differential　dependence　network　analyses　further　revealed　novel　rewiring　＇hubs＇　of　biological　networks　triggered　by　ATO　at　systems　level.　Functional　analyses　on　statistically　significant　networked　molecular　markers　confirmed　ATO＇s　role　as　an　effective　anti-proliferative　and　pro-apoptotic　drug,　in　vivo.　©　2012　IEEE.