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Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome
- Source :
- Proceedings of the National Academy of Sciences of the United States. Nov 25, 2008, Vol. 105 Issue 47, p18513, 6 p.
- Publication Year :
- 2008
-
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
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 105
- Issue :
- 47
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.190331750