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.
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References
Ridgway, J. et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444, 1083–1087 (2006)
Noguera-Troise, I. et al. Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444, 1032–1037 (2006)
Li, J. L. & Harris, A. L. Crosstalk of VEGF and Notch pathways in tumour angiogenesis: therapeutic implications. Front. Biosci. 14, 3094–3110 (2009)
Hicklin, D. J. Promoting angiogenesis to a fault. Nature Biotechnol. 25, 300–302 (2007)
Seton-Rogers, S. Tumour suppressors: Different roads to inactivation. Nature Rev. Cancer 7, 72 (2007)
ClinicalTrials.gov. A multiple-ascending-dose study of the safety and tolerability of REGN421 in patients with advanced solid malignancies 〈http://clinicaltrials.gov/ct2/show/NCT00871559〉 (Accessed, 7 January 2010)
ClinicalTrials.gov. A phase 1 dose escalation study of OMP-21M18 in subjects with solid tumors 〈http://clinicaltrials.gov/ct2/show/NCT00744562〉 (Accessed, 7 January 2010)
Schmidt, M. et al. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development 134, 2913–2923 (2007)
Hsieh, S. H. et al. Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene 27, 3746–3753 (2008)
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Yan, M., Callahan, C., Beyer, J. et al. Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6–E7 (2010). https://doi.org/10.1038/nature08751
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DOI: https://doi.org/10.1038/nature08751
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