Inhibition of FGF Receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody
| العنوان: | Inhibition of FGF Receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody |
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| المؤلفون: | Xiaodi Ren, Maria Malabunga, Ilhem Guernah, Qianxu Guo, Yongjun Yin, Craig Smith, Haijun Sun, David M. Ornitz, Nick Loizos, Nabil Chehab, Juqun Shen, Dale L. Ludwig, Yiwei Zhang |
| المصدر: | Disease Models & Mechanisms. |
| بيانات النشر: | The Company of Biologists, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | musculoskeletal diseases, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Fibroblast growth factor receptor 2, Fibroblast growth factor receptor 1, Neuroscience (miscellaneous), Medicine (miscellaneous), Fibroblast growth factor receptor 3, Biology, musculoskeletal system, medicine.disease, Fibroblast growth factor, medicine.disease_cause, Molecular biology, General Biochemistry, Genetics and Molecular Biology, stomatognathic diseases, 03 medical and health sciences, 030104 developmental biology, Immunology and Microbiology (miscellaneous), FGF9, medicine, Adenocarcinoma, Lung cancer, Carcinogenesis |
| الوصف: | Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, Fibroblast Growth Factor 9 (FGF9), a high affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC) specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11) with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumor-associated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3. |
| تدمد: | 1754-8411 1754-8403 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::83853f88a93d4e9b57d53e36f4467c7e https://doi.org/10.1242/dmm.024760 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........83853f88a93d4e9b57d53e36f4467c7e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17548411 17548403 |
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