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Chronic DLL4 blockade induces vascular neoplasms

Author

Listed:
  • 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)

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.

Suggested Citation

  • Minhong Yan & Christopher A. Callahan & Joseph C. Beyer & Krishna P. Allamneni & Gu Zhang & John Brady Ridgway & Kyle Niessen & Greg D. Plowman, 2010. "Chronic DLL4 blockade induces vascular neoplasms," Nature, Nature, vol. 463(7282), pages 6-7, February.
    • Handle: RePEc:nat:nature:v:463:y:2010:i:7282:d:10.1038_nature08751
    DOI: 10.1038/nature08751
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    Cited by:

    1. Monika A Jarzabek & William R Proctor & Jennifer Vogt & Rupal Desai & Patrick Dicker & Gary Cain & Rajiv Raja & Jens Brodbeck & Dale Stevens & Eric P van der Stok & John W M Martens & Cornelis Verhoef, 2018. "Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-20, June.

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