To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit macrophages migration. iVR1 was able to synergize with irinotecan determining a shrinkage of tumors that became undetectable after three weeks of combined treatment. Such treatment induced a significant prolongation of survival similar to that observed with bevacizumab and irinotecan combination. iVR1 also fully prevented lung invasion by HCT-116 cells injected in mouse tail vein. Also, iVR1 impressively inhibited choroid neovascularization after a single intravitreal injection. Collectively, data showed the strong potential of iVR1 peptide as a new anti-tumor and anti-metastatic agent and demonstrate the high flexibility of VEGFR1 antagonists as therapeutic anti-angiogenic agents in different pathological contexts.

Document Type


Publication Date


Notes/Citation Information

Published in Oncotarget, v. 6, no. 12, p. 10563-10576.

Copyright @ 2008-2016 Impact Journals, LLC. All rights reserved.

Licensed under a Creative Commons Attribution 3.0 License.

Digital Object Identifier (DOI)


Funding Information

This work was supported by AIRC (Associazione Italiana Ricerca sul Cancro) grant IG11420 and BioKer srl to S.D.F., Italian Ministry for Scientific Research, projects PON01_01434 to S.D.F. and PON01_1602 to M.R., and by NIH grants DP1GM114862, R01EY022238 and R01EY024068 to J.A.

3384-52558-1-SP.pdf (1815 kB)
Supplementary Figure

Included in

Ophthalmology Commons