Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose, and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments induced vascular regression and necrosis in tumor xenograft models, with highly glycolytic tumors becoming treatment resistant more rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments yielded an increase in both hypoxic and proliferative regions of tumors. A selection for highly glycolytic cells was noted and this metabolic shift was stable and associated with increased tumor aggressiveness and resistance to VEGF blockade in serially transplanted mice. Our results support the hypothesis that the highly glycolytic phenotype of tumor cells studied in xenograft models, either primary or secondary, is a cell-autonomous trait conferring resistance to VEGF blockade. The finding that metabolic traits of tumors can be selected by antiangiogenic therapy suggests insights into the evolutionary dynamics of tumor metabolism.

Curtarello, M., Zulato, E., Nardo, G., Valtorta, S., Guzzo, G., Rossi, E., et al. (2015). VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells. CANCER RESEARCH, 75(1), 120-133 [10.1158/0008-5472.CAN-13-2037].

VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells

Valtorta, Silvia;TODDE, SERGIO CAMILLO;MORESCO, ROSA MARIA;
2015

Abstract

Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose, and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments induced vascular regression and necrosis in tumor xenograft models, with highly glycolytic tumors becoming treatment resistant more rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments yielded an increase in both hypoxic and proliferative regions of tumors. A selection for highly glycolytic cells was noted and this metabolic shift was stable and associated with increased tumor aggressiveness and resistance to VEGF blockade in serially transplanted mice. Our results support the hypothesis that the highly glycolytic phenotype of tumor cells studied in xenograft models, either primary or secondary, is a cell-autonomous trait conferring resistance to VEGF blockade. The finding that metabolic traits of tumors can be selected by antiangiogenic therapy suggests insights into the evolutionary dynamics of tumor metabolism.
Articolo in rivista - Articolo scientifico
positron emission tomography, antiangiogenesis, glucose metabolism, hypoxia
English
2015
75
1
120
133
reserved
Curtarello, M., Zulato, E., Nardo, G., Valtorta, S., Guzzo, G., Rossi, E., et al. (2015). VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells. CANCER RESEARCH, 75(1), 120-133 [10.1158/0008-5472.CAN-13-2037].
File in questo prodotto:
File Dimensione Formato  
Curtarello-2015-Canc Res-VoR.pdf

Solo gestori archivio

Descrizione: Article
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Tutti i diritti riservati
Dimensione 2.59 MB
Formato Adobe PDF
2.59 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

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/10281/95805
Citazioni
  • Scopus 62
  • ???jsp.display-item.citation.isi??? 57
Social impact