The prototypical vascular targeting agent combretastatin A4 phosphate (CA4P) exerts its anti-angiogenic effect by targeting unstable budding tumor neo-vessels. CA4P is currently being studied in clinical trials in oncology.
In a paper appearing online on October 6 in advance of print publication of the November issue of the Journal of Clinical Investigation, Shahin Rafii and colleagues from Cornell University provide important mechanistic data demonstrating how CA4P has anti-tumor and anti-angiogenic activity.
The authors find that CA4P selectively targets endothelial cells (flat-shaped cells that make up the inside of blood vessels) but not smooth muscle cells (cells which surround most blood vessels), and induces regression of unstable, newly formed vessels by disruption of Vascular Endothelial-cadherin (VE-cadherin) signaling. VE-cadherin is a protein found at the junctions of overlapping regions of endothelial cells and plays a key role in many aspects of vascular function including, endothelial cell survival, cell migration, cell proliferation and assembly into vessel-like structures.
Dissecting the mechanism whereby CA4P exerts its anti-vascular effect will open up new avenues of research to selectively target tumor neo-vessels and increase the therapeutic window of anti-angiogenic agents.
TITLE: Combretastatin A4 phosphate disrupts tumor vasculature and growth by interfering with vascular endothelial-cadherin signaling
AUTHOR CONTACT:
Shahin Rafii
Weill Cornell Medical School, New York, NY USA
Phone: 212 746-2070; Fax: 212 746-8866; E-mail: srafii@med.cornell.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=24586
Journal
Journal of Clinical Investigation