HGG-05. GALLIUM MALTOLATE AS TREATMENT IN PEDIATRIC GLIOMA

Abstract Pediatric high-grade gliomas are devastating central nervous system tumors for which effective therapies are lacking. These tumors become rapidly resistant to chemotherapy or radiation therapy. We have shown that adult glioblastomas (U87, D54, and glioblastoma stem cells) have a high requirement for iron to support their growth and viability and that the metallodrug gallium maltolate, GaM, inhibits the growth of glioblastoma in vitro and in vivo in an orthotopic brain tumor rat model. Ga interacts with critical iron-dependent proteins to inhibit mitochondrial function and iron-dependent activity of ribonucleotide reductase. We have initiated investigations to explore the potential antineoplastic activity of GaM in pediatric glioma. Five different pediatric glioma cells lines: 3 glioblastoma (SJ-GBM2, SF188, CHLA-200) and two ATRT (CHLA-266 and CHLA-02) cell lines were incubated for 48 – 96 hours with increasing concentrations of GaM and the effect on cell proliferation was determined by MTT and PE assays. In CHLA-200, SF188, and SJ-GBM2 cells, the IC50 of GaM was 48.4 µM, 73.9 µM and 100 µM, respectively, while in CHLA-266 ATRT cells the IC50 was 16.3 µM after a 96h incubation of cells with GaM. Annexin V staining showed GaM, induces apoptosis in GBM and ATRT cells. Since the majority of glioma patients receive radiation therapy as their first line of treatment, we examined the effects of GaM on cell proliferation after glioma cell lines had been exposed to a single radiation dose of 10 GY. These studies indicate an additive effective of GaM on radiation-induced cell death. Our study is the first to show that GaM inhibits the growth of pediatric gliomas with varying efficacy. Further studies are in progress to investigate differences in iron metabolism among the pediatric glioma cells, drug combinations of GaM with other standard therapeutic agents, and the molecular basis for drug resistance.