Therapeutics: Glycogen synthase kinase 3β (GSK3B); ubiquitin specific peptidase 22 (USP22); lysine-specific demethylase 1 (LSD1; KDM1A)
Patient sample and mouse studies suggest that inhibiting the GSK3β-USP22-LSD1 axis could help treat glioblastoma multiforme (GBM) and other brain cancers. In tumor samples from GBM and astrocytoma patients, levels of GSK3β, USP22 and LSD1 correlated with tumor grade. In an orthotopic xenograft mouse model of GBM, shRNA targeting GSK3β, USP22 or LSD1 decreased tumor growth compared with scrambled shRNA. In two orthotopic xenograft mouse models of GBM, the GSK3β inhibitor tideglusib decreased tumor growth and increased survival, and tideglusib plus the generic chemotherapy temozolomide synergistically decreased tumor growth and increased survival compared with either agent alone. Next steps could include identifying and testing inhibitors of GSK3β, USP22 and LSD1 in animal models of other brain cancers.
Noscira S.A. and AMO Pharma Ltd. have tideglusib (AMO-02) in preclinical testing to treat myotonic dystrophy type I (DM1)...