J. Zimmermann, D. Obrecht, T. Remus
Dec 1, 2019
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Angiogenesis and Antiangiogenesis Agents
Abstract
Background: Balixafortide is a potent and selective antagonist of the chemokine receptor CXCR4, and is in PhIII for metastatic HER2-negative breast cancer in combination with eribulin (NCT03786094). Clinical proof-of concept of the combination with comparable tolerability to that of eribulin monotherapy was demonstrated in a recent PhI single arm dose-escalation trial (NCT01837095). Balixafortide can inhibit tumor growth through several mechanisms including chemosensitization in combination with chemotherapy (e.g. eribulin), suppression of metastasis, and activation of immune cell response in the tumor microenvironment. In addition, data regarding the co-regulation of the angiogenic factor VEGF and CXCR4 in colorectal cancer (CRC) tissue suggest a possible anti-angiogenic activity of Balixafortide. Methods: VEGF alpha-induced migration of endothelial cells and vascular permeabilization were assessed in vitro. Changes in VEGF alpha levels were determined in CXF260 CRC PDX tumor samples by Nanostring and in CXF260 cells in vitro by qPCR. Results: Balixafortide potently inhibited VEGF alpha-induced migration and permeabilization of an endothelial monolayer in vitro and reduced VEGF alpha levels in both, cultured CXF260 tumor cells in vitro and CXF260 tumors in vivo. Conclusions: Balixafortide modulates angiogenic mechanisms in vitro and in vivo and suggests further investigation of balixafortide in anti-angiogenic therapies. Citation Format: Johann Zimmermann, Daniel Obrecht, Tobias Remus. Anti-angiogenic activity of the CXCR4 antagonist balixafortide [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A003. doi:10.1158/1535-7163.TARG-19-A003