Matthew A Murray, Katelyn J Noronha, Yazhe Wang, Anna P Friedman, Sateja Paradkar, Hee-Won Suh, Ranjini K Sundaram, Charles Brenner, W Mark Saltzman, Ranjit S Bindra
The treatment of primary central nervous system (CNS) tumors is challenging due to the blood-brain barrier and complex mutational profiles, which is associated with low survival rates. However, recent studies have identified common mutations in gliomas (IDH-WT and mutant, WHO grades II-IV; with grade IV tumors referred to as glioblastomas; GBMs). These mutations drive epigenetic changes, leading to promoter methylation at the NAPRT gene locus, which encodes an enzyme involved in generating NAD+. Importantly, NAPRT-silencing introduces a therapeutic vulnerability to inhibitors targeting another NAD+ biogenesis enzyme, NAMPT, rationalizing a treatment for these malignancies...
May 1, 2024: Molecular Cancer Therapeutics