The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth
G Thurston, I Noguera-Troise… - Nature Reviews Cancer, 2007 - nature.com
G Thurston, I Noguera-Troise, GD Yancopoulos
Nature Reviews Cancer, 2007•nature.comAnti-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 …
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 …
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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