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Dll4-Notch signaling as a therapeutic target in tumor angiogenesis

Frank Kuhnert1, Jessica R Kirshner, Gavin Thurston

  • 1Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. Gavin.Thurston@regeneron.com.

Vascular Cell
|September 20, 2011
PubMed

Insights

Targeting the delta-like 4 (Dll4)-Notch pathway offers a new strategy against tumor angiogenesis, even for cancers resistant to anti-VEGF therapy. Dll4 blockade inhibits tumor growth by inducing non-productive blood vessel formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapy

Background:

  • Tumor angiogenesis is crucial for cancer growth and a key target for therapies, primarily involving the VEGF signaling pathway.
  • Clinical resistance to anti-VEGF therapies necessitates exploring alternative pathways to inhibit tumor angiogenesis.
  • The endothelial Notch ligand delta-like 4 (Dll4) is identified as a critical regulator of tumor angiogenesis.

Purpose of the Study:

  • To review the function of the Dll4-Notch signaling axis in tumor angiogenesis.
  • To discuss the potential of Dll4 as a therapeutic target for anti-angiogenesis cancer therapy.
  • To provide current perspectives as Dll4 inhibitors enter clinical trials.

Main Methods:

  • This review synthesizes current research on the Dll4-Notch signaling pathway in the context of tumor angiogenesis.
  • It analyzes the effects of Dll4 blockade on tumor vascularization and growth.
  • The review discusses findings from preclinical studies and emerging clinical trial data.

Main Results:

  • Blockade of Dll4-Notch signaling leads to excessive, non-productive tumor angiogenesis.
  • This aberrant angiogenesis has inhibitory effects on tumor growth.
  • Dll4-targeted therapy shows promise even in tumors resistant to anti-VEGF treatments.

Conclusions:

  • The Dll4-Notch signaling pathway is a vital target for novel anti-angiogenesis cancer therapies.
  • Targeting Dll4 offers a complementary or alternative strategy to anti-VEGF therapy.
  • Further clinical investigation of Dll4 inhibitors is warranted for cancer treatment.

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