Notch inhibitors for cancer treatment

Pharmacol Ther. 2013 Aug;139(2):95-110. doi: 10.1016/j.pharmthera.2013.02.003. Epub 2013 Feb 28.

Abstract

Notch signaling is an evolutionarily conserved cell signaling pathway involved in cell fate during development, stem cell renewal and differentiation in postnatal tissues. Roles for Notch in carcinogenesis, in the biology of cancer stem cells and tumor angiogenesis have been reported. These features identify Notch as a potential therapeutic target in oncology. Based on the molecular structure of Notch receptor, Notch ligands and Notch activators, a set of Notch pathway inhibitors have been developed. Most of these inhibitors had shown anti-tumor effects in preclinical studies. At the same time, the combinatorial effect of these inhibitors with current chemotherapeutical drugs is still under study in different clinical trials. In this review, we describe the basics of Notch signaling and the role of Notch in normal and cancer stem cells as a logic way to develop different Notch inhibitors and their current stage of progress for cancer patient's treatment.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Receptors, Notch / antagonists & inhibitors*
  • Receptors, Notch / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Receptors, Notch