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Review
. 2007 May;7(5):327-31.
doi: 10.1038/nrc2130.

The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth

Gavin Thurston  1 , Irene Noguera-Troise, George D Yancopoulos
Affiliations
Review

The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth

Gavin Thurston et al. Nat Rev Cancer. 2007 May.

Abstract

Anti-angiogenesis therapies have emerged as important treatment options for several types of tumours. To date, these therapies have focused on blocking the vascular endothelial growth factor (VEGF) pathway. A recent series of papers have shown that one ligand for the Notch receptors, Delta-like ligand 4 (DLL4), is normally induced by VEGF and is a negative-feedback regulator that restrains vascular sprouting and branching. Consistent with this role, the deletion or inhibition of DLL4 results in excessive, non-productive angiogenesis. This unrestrained angiogenesis unexpectedly and paradoxically decreases tumour growth, even in tumours resistant to anti-VEGF therapies. Can too much angiogenesis be bad for tumours but good for patients?

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