The WRN helicase: resolving a new target in microsatellite unstable cancers

Curr Opin Genet Dev. 2021 Dec:71:34-38. doi: 10.1016/j.gde.2021.06.014. Epub 2021 Jul 17.

Abstract

One of the goals of precision medicine is to uncover selective vulnerabilities in various cancers. A notable success has been the development of PARP inhibitors for the treatment of breast and ovarian cancers with mutations in BRCA genes. Only two years ago, it was discovered that cancers with microsatellite instability (MSI) were selectively dependent on the RecQ DNA helicase WRN. Subsequently, the molecular mechanism underlying WRN dependency in MSI cancers was uncovered. Here, we review how these developments have led to a promising new drug target in MSI cancers.

Publication types

  • Review

MeSH terms

  • Exodeoxyribonucleases / genetics
  • Humans
  • Microsatellite Instability*
  • Microsatellite Repeats
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism
  • Werner Syndrome Helicase / genetics

Substances

  • Exodeoxyribonucleases
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase