Chronic DLL4 blockade induces vascular neoplasms

Minhong Yan, Christopher A. Callahan, Joseph C. Beyer, Krishna P. Allamneni, Gu Zhang, John Brady Ridgway, Kyle Niessen and Greg D. Plowman
Additional contact information
Minhong Yan: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. minhong@gene.com
Christopher A. Callahan: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Joseph C. Beyer: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Krishna P. Allamneni: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
Gu Zhang: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. minhong@gene.com
John Brady Ridgway: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. minhong@gene.com
Kyle Niessen: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. minhong@gene.com
Greg D. Plowman: Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. minhong@gene.com

Nature, 2010, vol. 463, issue 7282, E6-E7

Abstract: Abstract Arising from: J. Ridgway et al. Nature 444, 1083–1087 (2006)10.1038/nature05313 Delta-like 4 (DLL4)-mediated Notch signalling has emerged as an attractive target for cancer therapy1,2. 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.

Date: 2010
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DOI: 10.1038/nature08751

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