Early Clinical Success of MTA-Cooperative PRMT5 Inhibitors for the Treatment of CDKN2A/MTAP-Deleted Cancers

Cancer Discov. 2023 Nov 1;13(11):2310-2312. doi: 10.1158/2159-8290.CD-23-0951.


CDKN2A encodes the tumor suppressors p16 and p14ARF and is the most common homozygously deleted gene in all human cancers; tumors frequently codelete the nearby gene MTAP, creating a dependency on PRMT5. In this issue of Cancer Discovery, Engstrom and colleagues report an MTA-cooperative PRMT5 methyltransferase inhibitor MRTX1719 that selectively kills CDKN2A/MTAP-codeleted cancers and demonstrates early efficacy in clinical trials for solid tumors harboring the CDKN2A/MTAP codeletion. See related article by Engstrom et al., p. 2412 (1).

Publication types

  • Comment

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Enzyme Inhibitors / therapeutic use
  • Gene Deletion
  • Genes, p16
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Protein-Arginine N-Methyltransferases / genetics


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Enzyme Inhibitors
  • PRMT5 protein, human
  • Protein-Arginine N-Methyltransferases