leptin and cediranib

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 chemotherapy versus chemotherapy with the small molecule VEGF receptors inhibitor cediranib identified circulating leptin levels, BMI, and a tumor metabolic and angiogenic gene expression signature associated 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 phosphorylation 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 findings suggest a link between patient physiology, tumor biology, and response to antiangiogenics, which may guide patient selection for VEGF therapy in the future.

Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Body Mass Index; Cell Line, Tumor; Colorectal Neoplasms; Humans; Kaplan-Meier Estimate; Leptin; Melanoma, Experimental; Mice; Mice, Obese; Proportional Hazards Models; Quinazolines; Retrospective Studies; Transcriptome; Treatment Outcome; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays