Repurposing antimalarial drug lumefantrine for glioblastoma

INDICATION: Brain cancer

The antimalarial drug lumefantrine, an FLI1 inhibitor, could treat glioblastoma resistant to radiation and temozolomide. A cell-based screen of compounds structurally related to approved and unapproved treatments for Ewing sarcoma, which is linked to the EWSR1-FLI1 fusion protein, for FLI1 inhibitors followed by in silico docking studies and additional cell-based inhibition assays yielded lumefantrine; the drug inhibited growth of two human glioblastoma cell lines with IC₅₀ values of 37.4 and 77.1 μM. Lumefantrine also blocked the cells’ migration and infiltration. In cultured radiation- and temozolomide-resistant glioblastoma cells, the drug inhibited growth with IC₅₀ values of 73.1-185.3 μM. In xenograft mouse models of glioblastoma resistant to radiation or temozolomide, lumefantrine reduced tumor growth. Next steps include testing lumefantrine in combination with other cancer therapies...