STAG2 identified as target in glioblastoma and Ewing sarcoma

INDICATION: Brain cancer; sarcoma

Cell culture studies suggest inhibiting STAG2 could sensitize glioblastoma and Ewing sarcoma to agents that disrupt repair of DNA double-strand (dsDNA) breaks. In two human glioblastoma and one human Ewing sarcoma cell line, STAG2 knockout in combination with an shRNA targeting one of five genes involved in dsDNA break repair -- ATR, BRCA1, RAD51, XRCC5 or PRKDC -- decreased growth compared with the shRNAs alone. Also in the cell lines, STAG2 knockout plus γ-irradiation, which causes DNA double-strand breaks, decreased growth compared with γ-irradiation alone. In the same lines, STAG2 knockout increased sensitivity to the chemotherapies and dsDNA break repair inhibitors gemcitabine, temozolomide, cisplatin, doxorubicin, topotecan, etoposide, Lynparza olaparib, Rubraca rucaparib, VX-970 and AZD6738 compared with normal STAG2 expression. Next steps could include testing STAG2 inhibition in combination with the drugs in animal models of glioblastoma and Ewing sarcoma...