Cancer synthetic vulnerabilities to protein arginine methyltransferase inhibitors

Curr Opin Pharmacol. 2021 Aug:59:33-42. doi: 10.1016/j.coph.2021.04.004. Epub 2021 May 27.

Abstract

Protein arginine methylation is an abundant post-translational modification involved in the modulation of essential cellular processes ranging from transcription, post-transcriptional RNA metabolism, and propagation of signaling cascades to the regulation of the DNA damage response. Excitingly for the field, in the past few years there have been remarkable advances in the development of molecular tools and clinical compounds able to selectively and potently inhibit protein arginine methyltransferase (PRMT) functions. In this review, we first discuss how the somatic mutations that confer advantages to cancer cells are often associated with vulnerabilities that can be exploited by PRMTs' inhibition. In a second part, we discuss strategies to uncover synthetic lethal combinations between existing therapies and PRMT inhibitors.

Keywords: MTAP; MYC; PRMTs; Splicing factor mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Arginine / genetics
  • Arginine / metabolism
  • Humans
  • Methylation
  • Neoplasms* / drug therapy
  • Protein Processing, Post-Translational
  • Protein-Arginine N-Methyltransferases* / genetics
  • Protein-Arginine N-Methyltransferases* / metabolism

Substances

  • Arginine
  • Protein-Arginine N-Methyltransferases