Chronic DLL4 blockade induces vascular neoplasms

Arising from: J. Ridgway et al. Nature 444, 1083-1087 (2006)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...

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Published in:Nature (London) 2010-02, Vol.463 (7282), p.E6-E7
Main Authors: Yan, Minhong, Callahan, Christopher A, Beyer, Joseph C, Allamneni, Krishna P, Zhang, Gu, Ridgway, John Brady, Niessen, Kyle, Plowman, Greg D
Format: Article
Language:English
Subjects:
631/92/609
692/699/67/1059/602
692/700/565/2194
Animals
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacology
brief-communications-arising
Care and treatment
Cell cycle
Chemical and Drug Induced Liver Injury - pathology
Chemical and Drug Induced Liver Injury - physiopathology
Endothelial Cells - drug effects
Endothelial Cells - pathology
Humanities and Social Sciences
Humans
Intracellular Signaling Peptides and Proteins - antagonists & inhibitors
Intracellular Signaling Peptides and Proteins - metabolism
Macaca fascicularis
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - metabolism
Mice
multidisciplinary
Physiological aspects
Proteins
Rats
Rattus
Receptors, Notch - metabolism
Risk factors
Rodents
Science
Science (multidisciplinary)
Signal Transduction
Studies
Tumors
Vascular Neoplasms - chemically induced
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Summary:Arising from: J. Ridgway et al. Nature 444, 1083-1087 (2006)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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature08751