3 results on '"I. Dabow"'
Number of results to display per page
Search Results
2. Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer
- Author
-
Daniel Rauh, Lukas C. Heukamp, Ingelore Baessmann, Silvia Querings, Roland T. Ullrich, C. Ligorio, Egbert F. Smit, Jonathan Weiss, Ines Dabow, Patrick Wagener, Jakob Schöttle, Stefania Damiani, Hannie Sietsma, Roopika Menon, Philippe Lorimier, Martin Peifer, Holger Moch, Thomas Zander, Roman K. Thomas, Walburga Engel-Riedel, Jörg Sänger, Franziska Gabler, Matthias Baumann, Steinar Sollberg, Hyatt Balke-Want, Matthew Conron, Peter Nürnberg, Stefanie Heynck, Christian Brambilla, Erich Stoelben, Zoe Wainer, Janine Altmüller, Rameen Beroukhim, Florian Fischer, Joachim H. Clement, Karen Ernestus, Iver Petersen, Federico Cappuzzo, Erik Thunnissen, Sascha Ansén, William Pao, Jürgen Wolf, Martin L. Sos, Mirjam Koker, Elisabeth Brambilla, Prudence A. Russell, Ben Solomon, Michael Hallek, Sebastian Maier, Alex Soltermann, Johannes M. Heuckmann, Harry J.M. Groen, Daniëlle A.M. Heideman, Reinhard Buettner, Gavin M. Wright, Corinna Ludwig, Sven Perner, Bert Klebl, Odd Terje Brustugun, Wim Timens, Frauke Leenders, Danila Seidel, J. Wei, M. L. So, D. Seidel, M. Peifer, T. Zander, J.M. Heuckmann, R. T. Ullrich, R. Menon, S. Maier, A. Soltermann, H. Moch, P. Wagener, F. Fischer, S. Heynck, M. Koker, J. Schöttle, F. Leender, F. Gabler, I. Dabow, S. Quering, L. C. Heukamp, H. Balke-Want, S.Ansén, D. Rauh, I. Baessmann, J. Altmüller, Z. Wainer, M. Conron, G. Wright, P. Russell, B. Solomon, E. Brambilla, C. Brambilla, P.Lorimier, S. Sollberg, O.Terje Brustugun, Walburga Engel-Riedel, Corinna Ludwig, Iver Petersen, J. Sänger, J. Clement, H. Groen, W. Timen, H. Sietsma, E. Thunnissen, E. Smit, D. Heideman, F.Cappuzzo, C. Ligorio, S.Damiani, M. Hallek, R. Beroukhim, W. Pao, B. Klebl, M. Baumann, R. Buettner, K. Ernestu, E. Stoelben, J. Wolf, P. Nürnberg, S. Perner, and R. K. Thomas, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Pathology, Pulmonary medicine, and CCA - Innovative therapy
- Subjects
Male ,Lung Neoplasms ,FGFR Inhibition ,Blotting, Western ,Mice, Nude ,Adenocarcinoma of Lung ,Apoptosis ,Biology ,Article ,SMOKE ASSOCIATED CANCER ,Cell Line ,GEFITINIB ,Mice ,Gefitinib ,TUMOR ,Carcinoma, Non-Small-Cell Lung ,medicine ,Anaplastic lymphoma kinase ,Animals ,Humans ,BREAST-CANCER ,Epidermal growth factor receptor ,Receptor, Fibroblast Growth Factor, Type 1 ,Enzyme Inhibitors ,Lung cancer ,IDENTIFICATION ,MUTATIONS ,Fibroblast growth factor receptor 1 ,KINASE INHIBITORS ,Cancer ,ADENOCARCINOMA ,General Medicine ,LUNG CANCER ,medicine.disease ,Xenograft Model Antitumor Assays ,GENE ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,Pyrimidines ,FGFR1 ,CARCINOMAS ,Cancer research ,biology.protein ,Adenocarcinoma ,RNA Interference ,SENSITIVITY ,medicine.drug - Abstract
Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
- Published
- 2010
- Full Text
- View/download PDF
3. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer.
- Author
-
Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schöttle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansén S, Rauh D, Baessmann I, Altmüller J, Wainer Z, Conron M, Wright G, Russell P, Solomon B, Brambilla E, Brambilla C, Lorimier P, Sollberg S, Brustugun OT, Engel-Riedel W, Ludwig C, Petersen I, Sänger J, Clement J, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman D, Cappuzzo F, Ligorio C, Damiani S, Hallek M, Beroukhim R, Pao W, Klebl B, Baumann M, Buettner R, Ernestus K, Stoelben E, Wolf J, Nürnberg P, Perner S, and Thomas RK
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma of Lung, Animals, Apoptosis genetics, Apoptosis physiology, Blotting, Western, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Cell Line, Enzyme Inhibitors therapeutic use, Gene Expression Regulation, Neoplastic genetics, Humans, Lung Neoplasms drug therapy, Male, Mice, Mice, Nude, Pyrimidines therapeutic use, RNA Interference, Receptor, Fibroblast Growth Factor, Type 1 antagonists & inhibitors, Receptor, Fibroblast Growth Factor, Type 1 genetics, Xenograft Model Antitumor Assays, Lung Neoplasms genetics, Lung Neoplasms metabolism, Receptor, Fibroblast Growth Factor, Type 1 metabolism
- Abstract
Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
- Published
- 2010
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.