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Crosstalk of VEGF and Notch pathways in tumour angiogenesis: therapeutic implications

Ji-Liang Li1, Adrian L Harris

  • 1Cancer Research UK Molecular Oncology Department, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK. ji-liang.li@imm.ox.ac.uk

Frontiers in Bioscience (Landmark Edition)
|March 11, 2009
PubMed

Insights

Blocking both VEGF and DLL4/Notch pathways synergistically inhibits tumor growth. Targeting DLL4/Notch signaling offers a promising new therapeutic strategy for various cancers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Angiogenesis, the formation of new blood vessels, is crucial for embryonic development and tumor growth.
  • Vascular Endothelial Growth Factor (VEGF) and Notch signaling pathways are key regulators of angiogenesis.
  • Anti-VEGF therapies are established treatments for several cancers, but resistance can develop.

Purpose of the Study:

  • To investigate the interplay between VEGF and DLL4/Notch signaling in angiogenesis.
  • To evaluate the therapeutic potential of combined blockade of VEGF and DLL4/Notch pathways in preclinical cancer models.

Main Methods:

  • Preclinical models were used to study the effects of blocking VEGF and DLL4/Notch signaling pathways.
  • Analysis of angiogenesis, tumor growth, and pathway interactions was performed.

Main Results:

  • DLL4/Notch signaling suppresses angiogenesis by inhibiting endothelial tip cell formation.
  • Blockade of DLL4/Notch signaling increases non-productive angiogenesis but reduces tumor growth, including VEGF-resistant tumors.
  • VEGF signaling induces DLL4/Notch signaling, and DLL4/Notch signaling modulates the VEGF pathway.
  • Combination therapy targeting both pathways synergistically inhibited tumor growth in preclinical models.

Conclusions:

  • VEGF and DLL4/Notch signaling pathways are intricately linked and act antagonistically in regulating angiogenesis.
  • Combined blockade of VEGF and DLL4/Notch pathways presents a promising synergistic strategy for cancer therapy.
  • Targeting DLL4/Notch signaling, despite being in early stages, holds potential for novel clinical applications in oncology.

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