Targeting DLL4 in tumors shows preclinical activity but potentially significant toxicity

Future Oncology
Ji-Liang LiA Harris

Abstract

Evaluation of: Yan M, Callahan CA, Beyer JC et al.: Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6-E7 (2010). Delta-like ligand 4 (DLL4) is a Notch ligand that is critical in the formation of a functional vascular network in tumors. Blockade of DLL4-mediated Notch signaling strikingly increases nonproductive angiogenesis, but significantly inhibits tumor growth in preclinical mouse models. Thus, DLL4 has emerged as an attractive target for cancer therapy. Anti-DLL4 antibodies have recently entered clinical trials. However, the potential toxic effects of anti-DLL4 are poorly understood. In this article, Yan et al. reported that chronic DLL4 blockade abnormally activates endothelial cells, causes pathological changes of multiple organs and induces vascular neoplasms. The findings need confirmation in further studies using different tumor-bearing animals but, nevertheless, raise important safety concerns regarding the use of anti-DLL4 agents and warrant monitoring for these effects in clinical trials for targeting DLL4.

References

Jan 19, 2002·Differentiation; Research in Biological Diversity·C MailhosD Ish-Horowicz
Nov 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicholas W GaleGeorge D Yancopoulos
Jun 1, 2005·Gene Expression Patterns : GEP·Rui Benedito, António Duarte
Aug 18, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nilay S PatelAdrian L Harris
Dec 22, 2006·Nature·Irene Noguera-TroiseGavin Thurston
Oct 1, 2008·The Journal of Experimental Medicine·Ute KochFreddy Radtke
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Ji-Liang Li, Adrian L Harris
Aug 12, 2009·Cell Stem Cell·Timothy HoeyAustin Gurney
Oct 22, 2009·British Journal of Cancer·A M JubbA L Harris
Feb 12, 2010·Nature·Minhong YanGreg D Plowman
Feb 20, 2010·The American Journal of Pathology·Adrian M JubbAdrian L Harris

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Citations

Sep 20, 2011·Vascular Cell·Frank KuhnertGavin Thurston
Apr 6, 2011·Future Oncology·Esther BridgesAdrian Harris
May 29, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Oran ErsterPatrick S Daugherty
Nov 23, 2011·Biochemical Society Transactions·Chern Ein Oon, Adrian L Harris
Nov 10, 2013·Circulation Research·Tara M Mleynek, Dean Li
May 24, 2017·Oncotarget·Sofia Nascimento Dos SantosEmerson Soares Bernardes
May 23, 2020·OncoTargets and Therapy·Meng-Xi XiuBo-Hai Kuang

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