Glycolytic phenotype and AMP kinase modify the pathologic response of tumor xenografts to VEGF neutralization.
Abstract VEGF antagonists are now widely used cancer therapeutics, but predictive biomarkers of response or toxicity remain unavailable. In this study, we analyzed the effects of anti-VEGF therapy on tumor metabolism and therapeutic response by using an integrated set of imaging techniques, including bioluminescence metabolic imaging, 18-fluorodeoxyglucose positron emission tomography, and MRI imaging and spectroscopy. Our results revealed that anti-VEGF therapy caused a dramatic depletion of glucose and an exhaustion of ATP levels in tumors, although glucose uptake was maintained. These metabolic changes selectively accompanied the presence of large necrotic areas and partial tumor regress…
VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells
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 met…
Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: Predictive value of DNA-PK and phosphorylated ACC
// Francesco Perrone 1,* , Gustavo Baldassarre 2,* , Stefano Indraccolo 3,* , Simona Signoriello 4 , Gennaro Chiappetta 1 , Franca Esposito 5 , Gabriella Ferrandina 6 , Renato Franco 1,15 , Delia Mezzanzanica 7 , Maura Sonego 2 , Elisabetta Zulato 3 , Gian F. Zannoni 6 , Vincenzo Canzonieri 2 , Giovanni Scambia 6 , Roberto Sorio 2 , Antonella Savarese 8 , Enrico Breda 9 , Paolo Scollo 10 , Antonella Ferro 11 , Stefano Tamberi 12 , Antonio Febbraro 13 , Donato Natale 14 , Massimo Di Maio 1,16 , Daniela Califano 1 , Giosue Scognamiglio 1 , Domenica Lorusso 7 , Silvana Canevari 7 , Simona Losito 1 , Ciro Gallo 4,** and Sandro Pignata 1,** 1 Istituto Nazionale per lo Studio e la Cura dei Tumor…