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

Kathleen M Mulvaney

doi:10.1158/2159-8290.CD-23-0951

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.

Author

Kathleen M Mulvaney^{1

2

3

4

5}

Affiliations

¹ Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, Virginia.
² Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia.
³ Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
⁴ Children's National Hospital, Center for Cancer and Immunology Research, Washington, DC.
⁵ Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, North Carolina.

PMID: 37909092
DOI: 10.1158/2159-8290.CD-23-0951

Abstract

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

Substances

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