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Anti-Dll4 therapy: can we block tumour growth by increasing angiogenesis?

Richard C A Sainson1, Adrian L Harris

  • 1Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK.

Trends in Molecular Medicine
|September 8, 2007
PubMed

Insights

Blocking the Dll4-Notch pathway unexpectedly promotes anti-cancer effects by causing nonfunctional tumor blood vessel growth. These novel agents offer a new approach to vascular targeting for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomedical Research

Background:

  • Tumor angiogenesis inhibition has been a cornerstone of cancer therapy since the 1970s.
  • The Dll4-Notch signaling pathway is crucial for regulating angiogenesis during development and is upregulated in cancer vasculature.

Purpose of the Study:

  • To investigate the effects of blocking Dll4 signaling in cancer.
  • To explore the therapeutic potential of Dll4-targeting agents.

Main Methods:

  • Development of molecules to block Dll4 signaling.
  • In vivo assessment of tumor growth and angiogenesis in response to Dll4 blockade.

Main Results:

  • Blocking Dll4 signaling unexpectedly inhibited tumor growth.
  • Inhibition was mediated by the induction of excessive, nonfunctional tumor angiogenesis.

Conclusions:

  • Molecules blocking Dll4 signaling represent a new class of pro-angiogenic, yet anticancer agents.
  • These agents offer a novel strategy for vascular targeting in cancer treatment.

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