VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells.
Cancer Res
; 75(1): 120-33, 2015 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-25381153
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Inibidores da Angiogênese
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Fator A de Crescimento do Endotélio Vascular
/
Neoplasias
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália