Sammanfattning

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.

Nyckelord

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

Publicerad i

Proceedings of the National Academy of Sciences
2008, Volym: 105, nummer: 47, sidor: 18513-18518
Utgivare: NATL ACAD SCIENCES

SLU författare

• Jones, Bernt

  • Institutionen för kliniska vetenskaper, Sveriges lantbruksuniversitet
    

Globala målen

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UKÄ forskningsämne

Cancer och onkologi


Publikationens identifierare

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

Permanent länk till denna sida (URI)

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