Chronic DLL4 blockade induces vascular neoplasms

M Yan, CA Callahan, JC Beyer, KP Allamneni, G Zhang… - Nature, 2010 - nature.com
M Yan, CA Callahan, JC Beyer, KP Allamneni, G Zhang, JB Ridgway, K Niessen…
Nature, 2010nature.com
Arising from: J. Ridgway et al. Nature444, 1083–1087 (2006) 10.1038/nature05313 Delta-
like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer
therapy,. However, the potential side effects of blocking this pathway remain uncertain. Here
we show that chronic DLL4 blockade causes pathological activation of endothelial cells,
disrupts normal organ homeostasis and induces vascular tumours, raising important safety
concerns.
Abstract
Arising from: J. Ridgway et al.Nature444, 1083–1087 (2006)10.1038/nature05313
Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy,. However, the potential side effects of blocking this pathway remain uncertain. Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising important safety concerns.
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