Chronic DLL4 blockade induces vascular neoplasms

Nature. 2010 Feb 11;463(7282):E6-7. doi: 10.1038/nature08751.

Abstract

Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy. However, the potential side effects of blocking this pathway remain uncertain. Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising important safety concerns.

Publication types

  • Comment

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Calcium-Binding Proteins
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Macaca fascicularis
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / metabolism
  • Mice
  • Rats
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Vascular Neoplasms / chemically induced*

Substances

  • Antineoplastic Agents
  • Calcium-Binding Proteins
  • DLL4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Notch