AIMS: Pancreatic ductal adenocarcinomas (PDACs) are chemoresistant, resulting in extremely poor survival of patients; therefore, novel molecular targets, even in small subsets of genetically characterized tumours, are urgently needed. Tyrosine kinase receptor inhibitors (TKIs) are already in clinical use. The aims of this study were to examine the gene copy number and expression of fibroblast growth factor receptor 1 (FGFR1) in 155 patients with PDAC, and investigate the effects of the FGFR-specific inhibitor BGJ398 on FGFR1-amplified pancreatic tumour cells in vitro. METHODS AND RESULTS: Fluorescence in-situ hybridization (FISH) and immunohistochemical analysis of 155 PDACs were performed using tissue microarrays. Amplification of FGFR1 was found in 2.6% (4/155) of cases. Four per cent of tumours (5/125) were shown to express FGFR1 by immunohistochemistry. Sequence analysis demonstrated an activating KRAS mutation (exon 2) in all FGFR1-amplified cases. The FGFR1-amplified pancreatic carcinoma cell line PT45P1 showed high levels of FGFR1 mRNA and protein expression. Proliferation of this cell line can be inhibited using the FGFR1 inhibitor BGJ398. CONCLUSIONS: FGFR1 represents a potential new therapeutic target in a subset of patients harbouring FGFR1-amplified tumours. Identification of pancreatic cancers harbouring FGFR1 amplification may be important in preselecting patients and/or interpreting clinical studies using TKIs.
AIMS: Pancreatic ductal adenocarcinomas (PDACs) are chemoresistant, resulting in extremely poor survival of patients; therefore, novel molecular targets, even in small subsets of genetically characterized tumours, are urgently needed. Tyrosine kinase receptor inhibitors (TKIs) are already in clinical use. The aims of this study were to examine the gene copy number and expression of fibroblast growth factor receptor 1 (FGFR1) in 155 patients with PDAC, and investigate the effects of the FGFR-specific inhibitor BGJ398 on FGFR1-amplified pancreatic tumour cells in vitro. METHODS AND RESULTS: Fluorescence in-situ hybridization (FISH) and immunohistochemical analysis of 155 PDACs were performed using tissue microarrays. Amplification of FGFR1 was found in 2.6% (4/155) of cases. Four per cent of tumours (5/125) were shown to express FGFR1 by immunohistochemistry. Sequence analysis demonstrated an activating KRAS mutation (exon 2) in all FGFR1-amplified cases. The FGFR1-amplified pancreatic carcinoma cell line PT45P1 showed high levels of FGFR1 mRNA and protein expression. Proliferation of this cell line can be inhibited using the FGFR1 inhibitor BGJ398. CONCLUSIONS:FGFR1 represents a potential new therapeutic target in a subset of patients harbouring FGFR1-amplified tumours. Identification of pancreatic cancers harbouring FGFR1 amplification may be important in preselecting patients and/or interpreting clinical studies using TKIs.
Authors: Min Joung Lee; Namju Kim; Ho-Kyung Choung; Ji-Young Choe; Sang In Khwarg; Ji Eun Kim Journal: J Cancer Res Clin Oncol Date: 2015-07-04 Impact factor: 4.553
Authors: Friederike Göke; Alina Franzen; Trista K Hinz; Lindsay A Marek; Petros Yoon; Rakesh Sharma; Maike Bode; Anne von Maessenhausen; Brigitte Lankat-Buttgereit; Antonia Göke; Carsten Golletz; Robert Kirsten; Diana Boehm; Wenzel Vogel; Emily K Kleczko; Justin R Eagles; Fred R Hirsch; Tobias Van Bremen; Friedrich Bootz; Andreas Schroeck; Jihye Kim; Aik-Choon Tan; Antonio Jimeno; Lynn E Heasley; Sven Perner Journal: Clin Cancer Res Date: 2015-05-26 Impact factor: 12.531