Cancer Dependencies: PRMT5 and MAT2A in MTAP/p16-Deleted Cancers

Discovery of targeted therapies that selectively exploit the genetic inactivation specific tumor suppressors remains a major challenge. This includes prevalent deletion CDKN2A/ MTAP locus, which was first reported nearly 40 years ago. The more recent advent RNA interference and functional genomic screening technologies led to identification hidden collateral lethalities occurring with passenger deletions in cancer cells. In particular, small-molecule inhibition type II arginine methyltransferase PRMT5 S-adenosylmethionine-producing enzyme MAT2A each presents precision medicine approach for treatment patients whose tumors have homozygous loss MTAP. this review, we highlight key aspects MTAP, PRMT5, biology provide conceptual framework developing novel therapeutic strategies summarize ongoing efforts drug MAT2A.