Therapeutics: GD3 ganglioside; ST8 α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (ST8SIA1); prominin 1 (PROM1; CD133)

Patient sample, cell culture and mouse studies suggest inhibiting GD3 ganglioside or its synthetic enzyme ST8SIA1 could help treat glioblastoma multiforme (GBM). In patients, tumor levels of GD3 ganglioside and ST8SIA1 correlated with disease progression, and in human GBM cell lines, levels of GD3 ganglioside correlated with expression of the cancer stem cell marker PROM1. In a human GBM cell line, an anti-GD3 ganglioside antibody increased apoptosis compared with a control antibody. In the same cell line, shRNA targeting ST8SIA1 decreased neurosphere formation compared with scrambled shRNA. In a xenograft mouse model of GBM, an anti-GD3 ganglioside antibody or tumor knockdown of ST8SIA1 decreased tumor growth compared with a control antibody or normal ST8SIA1 expression. Next steps could include testing anti-GD3 antibodies or ST8SIA1 inhibitors in additional models of glioblastoma. ...