Effective therapeutic targeting of the overexpressed HER-2 receptor in a highly metastatic orthotopic model of esophageal carcinoma.
| Autor: | Gros SJ; Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. sgros@uke.uni-hamburg.de, Kurschat N, Dohrmann T, Reichelt U, Dancau AM, Peldschus K, Adam G, Hoffman RM, Izbicki JR, Kaifi JT |
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| Jazyk: | angličtina |
| Zdroj: | Molecular cancer therapeutics [Mol Cancer Ther] 2010 Jul; Vol. 9 (7), pp. 2037-45. Date of Electronic Publication: 2010 Jul 06. |
| DOI: | 10.1158/1535-7163.MCT-10-0209 |
| Abstrakt: | This study aimed to determine the targeted efficacy of trastuzumab (Herceptin) on human epidermal growth factor receptor 2 (HER-2)-overexpressing metastatic esophageal cancer in an orthotopic mouse model. HER-2 overexpression and amplification of human esophageal primary and metastatic tumors were shown with HER-2-fluorescence in situ hybridization analysis and HER-2 immunostaining. Following orthotopic implantation with the HER-2-overexpressing OE19 human esophageal cancer cell line, mice were treated with trastuzumab. Sequential magnetic resonance imaging was used to monitor primary tumor and metastasis during treatment. After six weeks, a significant inhibition of primary tumor development was imaged in trastuzumab-treated animals in comparison with the control group. Trastuzumab treatment also led to a reduction of lymphatic metastasis. Thus, HER-2 targeted therapy with trastuzumab resulted in a significant primary tumor growth reduction as well as a decrease of lymph node metastases in the orthotopic model of metastatic esophageal carcinoma. The results of the present study suggest the clinical use of trastuzumab for HER-2-overexpressing esophageal cancer, which is a significant fraction of the patient population. Treatment of this highly treatment-resistant disease with trastuzumab in the adjuvant setting to prevent lymph node metastasis after primary tumor resection is suggested by the data in this report. ((c)2010 AACR.) |
| Databáze: | MEDLINE |
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