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.

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., 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>>, 2008; 105 (47): 18513-18518. [doi:10.1073/pnas.0807967105] [https://hdl.handle.net/10807/218407]

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

Lucchini, Franco;
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.
Inglese
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., 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>>, 2008; 105 (47): 18513-18518. [doi:10.1073/pnas.0807967105] [https://hdl.handle.net/10807/218407]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/218407
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 56
  • ???jsp.display-item.citation.isi??? ND
social impact