Wnt signaling inhibition confers induced synthetic lethality to PARP inhibitors

EMBO Mol Med. 2021 Apr 9;13(4):e14002. doi: 10.15252/emmm.202114002. Epub 2021 Mar 30.


Despite considerable efforts, therapeutic strategies targeting the Wnt pathway are still not clinically available. The pervasive role of Wnt-βcatenin signaling for the control of stem cells during normal tissue homeostasis makes the on-target toxicity of available therapeutic grade molecules an important limitation preventing their clinical introduction. The article in this issue of EMBO Molecular Medicine by Kaur et al (2021) reveals that treatment of Wnt-addicted cancer cells with inhibitors of Wnt signaling induces a state of BRCAness leading to hypersensitivity to PARP inhibitors. This is a new example of induced synthetic lethality that could pave the way for new indications for PARP inhibitors or may contribute to the long-awaited clinical introduction of therapeutic agents targeting the Wnt pathway.

Publication types

  • Comment

MeSH terms

  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Synthetic Lethal Mutations
  • Wnt Signaling Pathway* / drug effects


  • Poly(ADP-ribose) Polymerase Inhibitors