Abstract
Medulloblastoma is the most common malignant pediatric brain tumor that comprises at least 4 subgroups based on molecular characterization: WNT, SHH, group 3 and 4. Group 3 medulloblastoma is the most aggressive subtype with the worst prognosis due to its propensity to metastasize and resistance to therapy. Disulfiram (DSF) is a drug used in the treatment of chronic alcoholism that has been shown to have antineoplastic effects in a number of different cancers including glioblastoma. Its potency has been shown to be enhanced by copper. We tested two established medulloblastoma cell lines, UW228 and D425MED group 3 cells, and two primary cultures, IMB187 WNT and IMB226 SHH cells, for their sensitivity to DSF/Cu using the WST in vitro assay. We found that, whereas DSF on its own has little effect on medulloblastoma cells, in combination with a low concentration (350 nM) of Cu, which on its own has no effect, DSF strongly inhibited the viability of all tested medulloblastoma cells. The IC50 for DSF ranges between 60 nM and 230 nM, with UW228 cells being the most sensitive and the D425MED the least sensitive. DSF/Cu also has been shown to sensitize tumor cells to chemotherapy in a number of different settings. Studies to examine the therapeutic efficacy of DSF/Cu in the D425MED orthotopic animal model of medulloblastoma, both as monotherapy and in combination with the chemotherapeutic cisplatin, are in progress.