Therapeutic modulation of Notch signalling--are we there yet?

Nat Rev Drug Discov. 2014 May;13(5):357-78. doi: 10.1038/nrd4252.


The Notch signalling pathway is evolutionarily conserved and is crucial for the development and homeostasis of most tissues. Deregulated Notch signalling leads to various diseases, such as T cell leukaemia, Alagille syndrome and a stroke and dementia syndrome known as CADASIL, and so strategies to therapeutically modulate Notch signalling are of interest. Clinical trials of Notch pathway inhibitors in patients with solid tumours have been reported, and several approaches are under preclinical evaluation. In this Review, we focus on aspects of the pathway that are amenable to therapeutic intervention, diseases that could be targeted and the various Notch pathway modulation strategies that are currently being explored.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CADASIL / drug therapy
  • CADASIL / metabolism
  • Clinical Trials as Topic / methods
  • Clinical Trials as Topic / trends
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends
  • Humans
  • Leukemia / drug therapy
  • Leukemia / metabolism
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / metabolism
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*


  • RNA, Small Interfering
  • Receptors, Notch