Summary
PROJECT SUMMARY/ABSTRACT MTAP is deleted in approximately 15% of all human malignancies and co-occurs in 80-90% of all CDKN2A- /CDKN2B-deleted cancers, including but not limited to cancers of the lung, gastric system, brain, breast, urinary tract, and skin. The inhibition of PRMT5, an arginine methyltransferase (PRMT), is synthetic lethal to cancer cells with MTAP loss. MTAP loss elevates the level of intracellular methylthioadenosine (MTA), which binds and potently inhibits PRMT5 activity via competing with S-adenosylmethionine (SAM) binding. This creates a state whereby MTAP-loss cancer cell
