Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome

Abstract

The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer-associated systemic syndrome (CASS) and prevented death in tumor-bearing mice. Surprisingly, VIEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that "off-tumor" VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model over-expressing neu. Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs.

Keywords

angiogenesis; antiangiogenic therapy; cancer syndrome; tumor growth; VEGF

Published in

Proceedings of the National Academy of Sciences
2008, Volume: 105, number: 47, pages: 18513-18518
Publisher: NATL ACAD SCIENCES

SLU Authors

• Jones, Bernt

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

Sustainable Development Goals

SDG3 Good health and well-being


UKÄ Subject classification

Cancer and Oncology


Publication identifier

DOI: https://doi.org/10.1073/pnas.0807967105

Permanent link to this page (URI)

https://res.slu.se/id/publ/26144