1. Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome
- Author
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Xue, Yuan, Religa, Piotr, Cao, Renhai, Hansen, Anker Jon, Lucchini, Franco, Jones, Bernt, Wu, Yan, Zhu, Zhenping, Pytowski, Bronislaw, Liang, Yuxiang, Zhong, Weide, Vezzoni, Paolo, Rozell, Bjorn, and Cao, Yihai
- Subjects
Angiogenesis inhibitors -- Research ,Vascular endothelial growth factor -- Properties ,Transforming growth factors -- Research ,Neovascularization -- Research ,Cancer -- Research ,Oncology, Experimental ,Science and technology - 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-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs. angiogenesis | antiangiogenic therapy | cancer syndrome | tumor growth | VEGF
- Published
- 2008