Team ties target to GBM progression, identifies biomarker
In a paper published in Cancer Cell, researchers at Massachusetts Institute of Technology and Harvard Medical School used an in vivo short hairpin RNA screen to identify an epigenetic regulator, protein arginine methyltransferase 5 (PRMT5), as a driver of glioblastoma progression and uncovered a potential biomarker to identify tumors that are insensitive to PRMT5 inhibition.
The team determined that genetic and pharmacologic inhibition of PRMT5 with EPZ015666 from Epizyme Inc. (NASDAQ:EPZM) diminished the growth of glioblastomas in vivo in mice and in cell culture. Increased expression and activity of PRMT5 has been linked to several cancers; however, the mechanism by which PRMT5 contributes to tumor progression is unclear. Further cell culture studies suggest that inhibition of PRMT5 in glioblastoma cells restricts tumor growth by increasing the number of detained introns in cell cycle transcripts, thereby decreasing corresponding protein expression...