Cetuximab May Inhibit Tumor Growth and Angiogenesis Induced by Ionizing Radiation: A Preclinical Rationale for Maintenance Treatment After Radiotherapy
| Autor: | Agnès Figueras, A. Lozano, Silvia Vazquez, Gemma Pueyo, Marta Baro, Josep Balart, Gabriel Capellá, Ricard Mesia |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Angiogenesis medicine.medical_treatment EGFR Cetuximab Angiogenesis Inhibitors Antineoplastic Agents Antibodies Monoclonal Humanized Mice Head And Neck Cancers Cell Line Tumor medicine Animals Humans Epidermal growth factor receptor Protein kinase B Cell Proliferation biology Radiotherapy business.industry Cell growth Growth factor Antibodies Monoclonal Neoplasms Experimental Combined Modality Therapy Xenograft Model Antitumor Assays digestive system diseases ErbB Receptors Radiation therapy Ki-67 Antigen Oncology Cytoprotection Cancer research biology.protein Maintenance therapy business Transforming growth factor medicine.drug |
| Zdroj: | ONCOLOGIST r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1083-7159 |
| Popis: | Background. The benefits of radiotherapy and cetuximab have encouraged evaluation of cetuximab after radiotherapy. The aims of this study were to preclinically evaluate the efficacy of cetuximab maintenance after radiotherapy and eventually determine its mechanisms of action. Methods. The A431 human carcinoma cell line was treated in culture with fractionated radiotherapy and cetuximab. The surviving cells were injected s.c. into nude mice to mimic microscopic residual disease. The animals were randomized to receive either cetuximab or saline solution. Tumor growth, cell proliferation (Ki-67), microvessel density (MVD), epidermal growth factor receptor (EGFR) and transforming growth factor (TGF-α) mRNA transcription, and vascular endothelial growth factor (VEGF) secretion were measured. Results. Tumors from irradiated cells had a faster growth rate, higher Ki-67 index, and greater angiogenesis than tumors from untreated cells. This aggressive phenotype was associated with in vitro radiation-induced extracellular signal–related kinase (ERK)-1/2 and Akt activation, greater EGFR and TGF-α transcription, and augmented VEGF secretion, all of which were inhibited by cetuximab. In cetuximab-treated mice with tumors arising from irradiated cells, time to volume was longer by a factor of 3.52, whereas the Ki-67 index and MVD were 1.57 and 1.49 times lower, respectively, a larger enhancement than seen in tumors from untreated cells. These findings suggest that cells surviving radiation may express factors that promote cell survival and induce an aggressive phenotype that may potentially be blocked by cetuximab maintenance therapy. Conclusions. These results support the clinical evaluation of adjuvant therapy with cetuximab after radiotherapy in EGFR-dependent carcinomas. |
| Databáze: | OpenAIRE |
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