Chronic DLL4 blockade induces vascular neoplasms - PubMed (original) (raw)

Comment

. 2010 Feb 11;463(7282):E6-7.

doi: 10.1038/nature08751.

Affiliations

• PMID: 20147986
• DOI: 10.1038/nature08751

Comment

Chronic DLL4 blockade induces vascular neoplasms

Minhong Yan et al. Nature. 2010.

Abstract

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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Comment in

• Targeting DLL4 in tumors shows preclinical activity but potentially significant toxicity.
  Li JL, Jubb AM, Harris AL. Li JL, et al. Future Oncol. 2010 Jul;6(7):1099-103. doi: 10.2217/fon.10.62. Future Oncol. 2010. PMID: 20624122

Comment on

• Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis.
  Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y, Kowalski J, Watts RJ, Callahan C, Kasman I, Singh M, Chien M, Tan C, Hongo JA, de Sauvage F, Plowman G, Yan M. Ridgway J, et al. Nature. 2006 Dec 21;444(7122):1083-7. doi: 10.1038/nature05313. Nature. 2006. PMID: 17183323

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References

1. 1. Development. 2007 Aug;134(16):2913-23 - PubMed
2. 1. Nat Rev Cancer. 2009 Sep;9(9):610 - PubMed
3. 1. Oncogene. 2008 Jun 12;27(26):3746-53 - PubMed
4. 1. Nat Biotechnol. 2007 Mar;25(3):300-2 - PubMed
5. 1. Front Biosci (Landmark Ed). 2009 Jan 01;14:3094-110 - PubMed

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