Related Experiment Video

Updated: Jul 9, 2026

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

Delta-like 4/Notch signaling and its therapeutic implications

Minhong Yan1, Greg D Plowman

  • 1Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, CA 94080, USA. minhong@gene.com

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|December 21, 2007
PubMed

Insights

Targeting Delta-like 4 (Dll4)-mediated Notch signaling, a key pathway in angiogenesis, shows promise for cancer therapy. Blocking Dll4/Notch signaling inhibits tumor growth by creating defective vasculature, offering a new strategy against treatment resistance.

Area of Science:

  • Molecular biology
  • Cancer research
  • Vascular biology

Background:

  • Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and a target for cancer therapies.
  • Vascular endothelial growth factor (VEGF) signaling is a validated target, with bevacizumab approved for certain cancers.
  • Delta-like 4 (Dll4)-mediated Notch signaling is another critical pathway in vascular development and angiogenesis.

Purpose of the Study:

  • To explore the role of Dll4-mediated Notch signaling in angiogenesis and its potential as a cancer therapy target.
  • To understand the consequences of Dll4/Notch signaling attenuation on tumor vasculature and growth.

Main Methods:

  • Review of recent studies on Dll4 function in angiogenesis.
  • Analysis of preclinical data on the effects of Dll4/Notch signaling blockade.

Main Results:

  • Dll4 acts downstream of VEGF, providing negative feedback on VEGF signaling.
  • Attenuation of Dll4/Notch signaling leads to chaotic vascular networks with excessive sprouting.
  • Blocking Dll4/Notch signaling paradoxically increases tumor vessel density but inhibits tumor growth due to defective vasculature.

Conclusions:

  • Dll4/Notch signaling blockade is a promising strategy for antiangiogenesis cancer therapy.
  • This approach may be particularly effective in overcoming resistance to existing therapies.

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