Leptin, BMI, and a Metabolic Gene Expression Signature Associated with Clinical Outcome to VEGF Inhibition in Colorectal Cancer
| Autor: | Mark Wappett, Jeremy Frith, Jane Kendrew, Bhavika Patel, Catherine Anne Eberlein, Susan E. Critchlow, Paul D. Smith, Jane Robertson, Simon T. Barry, Aurelien J.C. Pommier, Russell D. J. Huby, Christopher Womack, Hayley Campbell, Shethah Morgan, Neil R. Smith, Filippos Michopoulos, Matthew Farren |
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| Rok vydání: | 2016 |
| Předmět: |
Leptin
Vascular Endothelial Growth Factor A 0301 basic medicine Colorectal cancer Physiology medicine.medical_treatment Melanoma Experimental Mice Obese Antineoplastic Agents Kaplan-Meier Estimate Biology Body Mass Index Cediranib Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Biomarkers Tumor medicine Animals Humans Molecular Biology Proportional Hazards Models Retrospective Studies Chemotherapy Melanoma Cancer Cell Biology medicine.disease Xenograft Model Antitumor Assays 3. Good health Vascular endothelial growth factor Vascular endothelial growth factor A Treatment Outcome 030104 developmental biology chemistry 030220 oncology & carcinogenesis Quinazolines Cancer research Colorectal Neoplasms Transcriptome medicine.drug |
| Zdroj: | Cell Metabolism. 23(1):77-93 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2015.10.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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