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Autre Publication Scientifique Cell Metabolism Année : 2015

Leptin, BMI, and a Metabolic Gene Expression Signature Associated with Clinical Outcome to VEGF Inhibition in Colorectal Cancer

Résumé

VEGF (vascular endothelial growth factor) signaling inhibitors are widely used in different cancer types; however, patient selection remains a challenge. Analyses of samples from a phase III clinical trial in metastatic colorectal cancer testing chemo- therapy versus chemotherapy with the small mole- cule VEGF receptors inhibitor cediranib identified circulating leptin levels, BMI, and a tumor metabolic and angiogenic gene expression signature asso- ciated with improved clinical outcome in patients treated with cediranib. Patients with a glycolytic and hypoxic/angiogenic profile were associated with increased benefit from cediranib, whereas patients with a high lipogenic, oxidative phosphory- lation and serine biosynthesis signature did not gain benefit. These findings translated to pre-clinical tumor xenograft models where the same metabolic gene expression profiles were associated with in vivo sensitivity to cediranib as monotherapy. These find- ings suggest a link between patient physiology, tumor biology, and response to antiangiogenics, which may guide patient selection for VEGF therapy in the future.
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Dates et versions

hal-04622737 , version 1 (24-06-2024)

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Aurélien J C Pommier, Matthew Farren, Bhavika Patel, Mark Wappett, Filippos Michopoulos, et al.. Leptin, BMI, and a Metabolic Gene Expression Signature Associated with Clinical Outcome to VEGF Inhibition in Colorectal Cancer. 2015, pp.77 - 93. ⟨10.1016/j.cmet.2015.10.015⟩. ⟨hal-04622737⟩
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