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.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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