Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of Glioblastoma

Dilsulfiram together with Copper shows efficacy against patient derived Brain Tumor Initiating Cells (BTICs) in vitro and sensitizes BTICs to the DNA damaging agent TMZ. In addition, preclinical assessment found that DSF/Cu potentiaties the efficicacy of TMZ in vivo and prolongs survival. We used microarrays to detail the global profile of gene expression underlying DSF/Cu treatment in vitro and in vivo in BTICs. BTICs grown in brain tumor stem cels media containing EGF and FGF were treated with DSF (50nM) and Cu (1uM) together for 12 hrs. Cells were then collected and prepared for gene expression analysis. For the in vivo study, 4 wks after BT147 was implanted into the brain of CB17 SCID mice, animals were treated with control vehicle (oral-plus) or DSF (100mg/kg) daily via oral administration for two weeks (5 days on, two days off) and Copper (2mg/kg) daily via oral administartion for two weeks. Animals were then sacrificed and the brain tumor tissue was collected and prepared for gene expression analysis.