Inhibitory Effect of PRMT5/MTA Inhibitor on MTAP-Deficient Glioma May Be Influenced by Surrounding Normal Cells.

ABSTRACT:

Background

Methylthioadenosine phosphorylase (MTAP) and protein arginine methyltransferase 5 (PRMT5) are considered to be a synthetic lethal pair of targets, due to the fact that deletion of MTAP leads to massive production of methylthioadenosine (MTA) decreasing the activity of PRMT5. In vitro and in vivo experiments have demonstrated that MRTX1719, a small molecule that selectively binds PRMT5/MTA complex, significantly inhibits the proliferation of MTAP-deficient tumors and has a weak toxic effect on normal cells. However, it has been reported that MTAP-deleted tumors did not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma, which might lead to a diminished anti-cancer effect of MRTX1719.

Methods

We first analyzed whether there were

SUBMITTER: Wang Y 

PROVIDER: S-EPMC11664235 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature