Abstract：
: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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Pommier AJ,Farren M,Patel B,Wappett M,Michopoulos F,Smith NR,Kendrew J,Frith J,Huby R,Eberlein C,Campbell H,Womack C,Smith PD,Robertson J,Morgan S,Critchlow SE,Barry STdoi
10.1016/j.cmet.2015.10.015subject
Has Abstractpub_date
2016-01-12 00:00:00pages
77-93issue
1eissn
1550-4131issn
1932-7420pii
S1550-4131(15)00531-8journal_volume
23pub_type
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