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Status: Bibliographieeintrag

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Verfasst von:Chudasama, Priya [VerfasserIn]   i
 Renner, Marcus [VerfasserIn]   i
 Alldinger, Ingo [VerfasserIn]   i
 Schimmack, Simon [VerfasserIn]   i
 Jäger, Dirk [VerfasserIn]   i
 Kalle, Christof von [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Heining, Christoph [VerfasserIn]   i
 Gröschel, Stefan [VerfasserIn]   i
 Glimm, Hanno [VerfasserIn]   i
 Mechtersheimer, Gunhild [VerfasserIn]   i
 Fröhling, Stefan [VerfasserIn]   i
Titel:Targeting fibroblast growth factor receptor 1 for treatment of soft-tissue sarcoma
Verf.angabe:Priya Chudasama, Marcus Renner, Melanie Straub, Sadaf S. Mughal, Barbara Hutter, Zeynep Kosaloglu, Ron Schweßinger, Matthias Scheffler, Ingo Alldinger, Simon Schimmack, Thorsten Persigehl, Carsten Kobe, Dirk Jäger, Christof von Kalle, Peter Schirmacher, Marie-Kristin Beckhaus, Stephan Wolf, Christoph Heining, Stefan Gröschel, Jürgen Wolf, Benedikt Brors, Wilko Weichert, Hanno Glimm, Claudia Scholl, Gunhild Mechtersheimer, Katja Specht and Stefan Fröhling
E-Jahr:2017
Jahr: February 2017
Umfang:12 S.
Fussnoten:Gesehen am 24.07.2018
Titel Quelle:Enthalten in: Clinical cancer research
Ort Quelle:Philadelphia, Pa. [u.a.] : AACR, 1995
Jahr Quelle:2017
Band/Heft Quelle:23(2017), 4, Seite 962-973
ISSN Quelle:1557-3265
Abstract:Purpose: Altered FGFR1 signaling has emerged as a therapeutic target in epithelial malignancies. In contrast, the role of FGFR1 in soft-tissue sarcoma (STS) has not been established. Prompted by the detection and subsequent therapeutic inhibition of amplified FGFR1 in a patient with metastatic leiomyosarcoma, we investigated the oncogenic properties of FGFR1 and its potential as a drug target in patients with STS. Experimental Design: The frequency of FGFR1 amplification and overexpression, as assessed by FISH, microarray-based comparative genomic hybridization and mRNA expression profiling, SNP array profiling, and RNA sequencing, was determined in three patient cohorts. The sensitivity of STS cell lines with or without FGFR1 alterations to genetic and pharmacologic FGFR1 inhibition and the signaling pathways engaged by FGFR1 were investigated using viability assays, colony formation assays, and biochemical analysis.Results: Increased FGFR1 copy number was detected in 74 of 190 (38.9%; cohort 1), 13 of 79 (16.5%; cohort 2), and 80 of 254 (31.5%; cohort 3) patients. FGFR1 overexpression occurred in 16 of 79 (20.2%, cohort 2) and 39 of 254 (15.4%; cohort 3) patients. Targeting of FGFR1 by RNA interference and small-molecule inhibitors (PD173074, AZD4547, BGJ398) revealed that the requirement for FGFR1 signaling in STS cells is dictated by FGFR1 expression levels, and identified the MAPK-ERK1/2 axis as critical FGFR1 effector pathway.Conclusions: These data identify FGFR1 as a driver gene in multiple STS subtypes and support FGFR1 inhibition, guided by patient selection according to the FGFR1 expression and monitoring of MAPK-ERK1/2 signaling, as a therapeutic option in this challenging group of diseases. Clin Cancer Res; 23(4); 962-73. ©2016 AACR.
DOI:doi:10.1158/1078-0432.CCR-16-0860
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Kostenfrei: Volltext ; Verlag: http://dx.doi.org/10.1158/1078-0432.CCR-16-0860
 Kostenfrei: Volltext: http://clincancerres.aacrjournals.org/content/23/4/962
 DOI: https://doi.org/10.1158/1078-0432.CCR-16-0860
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1577873793
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