Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression
| Autor: | Otto C. Boerman, Hanneke W. M. van Laarhoven, Sandra Heskamp, Mallory S. Engelhardt, Janneke D.M. Molkenboer-Kuenen, Anneke Geurts-Moespot, Fred C.G.J. Sweep, Winette T. A. van der Graaf, Wim J.G. Oyen |
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| Přispěvatelé: | Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Oncology |
| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
Oncology genetic structures Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] medicine.medical_treatment Cetuximab Pharmaceutical Science Multimodal Imaging Immunoenzyme Techniques Mice Antineoplastic Combined Chemotherapy Protocols Drug Discovery Tumor Cells Cultured Molecular Targeted Therapy Mice Inbred BALB C Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] Bevacizumab ErbB Receptors Molecular Medicine Female Nanomedicine Radboud Institute for Health Sciences [Radboudumc 19] medicine.drug Biodistribution medicine.medical_specialty Mice Nude Breast Neoplasms Enzyme-Linked Immunosorbent Assay Vegf expression Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] Antibodies Monoclonal Humanized Advanced colorectal cancer Internal medicine medicine Animals Humans Tumor growth neoplasms Chemotherapy business.industry Cancer medicine.disease Xenograft Model Antitumor Assays eye diseases digestive system diseases sense organs business Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] |
| Zdroj: | Molecular Pharmaceutics, 11, 4249-4257 Molecular Pharmaceutics, 11, pp. 4249-4257 Molecular pharmaceutics, 11(11), 4249-4257. American Chemical Society |
| ISSN: | 1543-8392 1543-8384 4249-4257 |
| DOI: | 10.1021/mp500460g |
| Popis: | Item does not contain fulltext Introduction: Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of cetuximab on VEGF expression and targeting of bevacizumab to the tumor. Material and methods: Mice with subcutaneous SUM149 or WiDr xenografts were treated with cetuximab, bevacizumab or the combination. Before start of cetuximab treatment, and after 7 and 21 days of treatment, the uptake of radiolabeled bevacizumab in the tumor was measured by immunoSPECT/CT. Results: Tumor growth of SUM149 xenografts was significantly inhibited by cetuximab, bevacizumab or the combination, while growth of WiDr xenografts was not affected. Cetuximab caused a significant reduction of bevacizumab uptake in SUM149 xenografts, while tumor-to-blood ratios in mice with WiDr xenografts did not change. Biodistribution studies with an irrelevant antibody in the SUM149 model also showed significantly reduced tumor-to-blood ratios. Cetuximab treatment did not decrease VEGF expression. Conclusion: Without decreasing VEGF levels, cetuximab reduces tumor targeting of bevacizumab. This could at least partly explain why the combination of bevacizumab and cetuximab does not result in improved therapeutic efficacy. |
| Databáze: | OpenAIRE |
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