Targeting protein arginine methyltransferase 5 sensitizes glioblastoma to trametinib.

ABSTRACT:

Background

The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM.

Methods

Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were t

SUBMITTER: Banasavadi-Siddegowda YK 

PROVIDER: S-EPMC9297944 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature