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

Yuan Xue, Piotr Religa, Renhai Cao, Anker Jon Hansen, Franco Lucchini, Bernt Jones, Yan Wu, Zhenping Zhu, Bronislaw Pytowski, Yuxiang Liang, Weide Zhong, Paolo Vezzoni, Björn Rozell, Yihai Cao

Research output: Contribution to journalArticle

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, VEGFR2 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 overexpressing neu. Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGFagentsandprovide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs.

Original languageEnglish
Pages (from-to)18513-18518
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number47
DOIs
Publication statusPublished - Nov 25 2008

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Keywords

  • Angiogenesis
  • Antiangiogenic therapy
  • Cancer syndrome
  • Tumor growth
  • VEGF

ASJC Scopus subject areas

  • General

Cite this

Xue, Y., Religa, P., Cao, R., Hansen, A. J., Lucchini, F., Jones, B., Wu, Y., Zhu, Z., Pytowski, B., Liang, Y., Zhong, W., Vezzoni, P., Rozell, B., & Cao, Y. (2008). Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome. Proceedings of the National Academy of Sciences of the United States of America, 105(47), 18513-18518. https://doi.org/10.1073/pnas.0807967105