Valentina Fogal, Filippos Michopoulos, Andrew F Jarnuczak, Ghaith M Hamza, Stephanie Harlfinger, Paul Davey, Heather Hulme, Stephen J Atkinson, Piotr Gabrowski, Tony Cheung, Michael Grondine, Clare Hoover, Jonathan Rose, Chandler Bray, Alison J Foster, Sean Askin, Muntasir Mamun Majumder, Paul Fitzpatrick, Eric Miele, Ruth Macdonald, Hector C Keun, Muireann Coen
The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine...
May 17, 2024: Archives of Toxicology