Complexity of FGFR signalling in metastatic urothelial cancer.

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• dc.contributor.author Rodriguez-Vida, Alejoca
• dc.contributor.author Saggese, Matildeca
• dc.contributor.author Hughes, Simonca
• dc.contributor.author Rudman, Sarahca
• dc.contributor.author Chowdhury, Simonca
• dc.contributor.author Smith, Neil R.ca
• dc.contributor.author Lawrence, Peterca
• dc.contributor.author Rooney, Claireca
• dc.contributor.author Dougherty, Brianca
• dc.contributor.author Landers, Donalca
• dc.contributor.author Kilgour, Elaineca
• dc.contributor.author Arkenau, Hendrik-Tobiasca
• dc.date.accessioned 2016-02-03T09:59:25Z
• dc.date.available 2016-02-03T09:59:25Z
• dc.date.issued 2015
• dc.description.abstract BACKGROUND: Urothelial cancers (UC) are the fourth most common tumours worldwide after prostate (or breast), lung and colorectal cancer. Despite recent improvements in their management, UC remain an aggressive disease associated with a poor outcome. Following disease progression on first-line platinum-based chemotherapy, very few effective treatment options are available and none of them have shown significant improvement in overall survival. Alterations of the fibroblast growth factor receptor (FGFR) pathway including amplification, mutations and overexpression are common in UC. Pre-clinical data suggest that the presence of such dysregulations may confer sensitivity to FGFR inhibitors. MATERIALS AND METHODS: We present here the case of a patient with a metastatic UC of the renal pelvis with lymph node metastases treated with the selective FGFR inhibitor AZD4547. RESULTS: To date, the patient has been on a study drug for 32 months with acceptable tolerance and maintained radiological partial response as per RECIST 1.1 criteria. Exploratory biomarker analysis showed FGFR3, FGFR1, FGF-ligand and fibroblast growth factor receptor substrate 2 (FRS2) expression in the patient's tumour, together with the presence of a germ-line mutation in the FGFR3 extracellular binding domain. This is not a known hotspot mutation, and the functional significance remains unclear. CONCLUSIONS: The FGFR inhibitor AZD4547 exhibits antitumour activity in a metastatic urothelial cancer displaying FGFR1, FGFR3, FGF-ligand and FRS2 expression. This lends support to the further exploration of FGFR inhibitors in urothelial cancer. Further studies are required to determinate the most effective way to select those patients most likely to respond.ca
• dc.format.mimetype application/pdfca
• dc.identifier.citation Rodriguez-Vida A, Saggese M, Hughes S, Rudman S, Chowdhury S, Smith NR. et al. Complexity of FGFR signalling in metastatic urothelial cancer. J Hematol Oncol. 2015 Oct 24;8(1):119. doi: 10.1186/s13045-015-0221-6.ca
• dc.identifier.doi http://dx.doi.org/10.1186/s13045-015-0221-6
• dc.identifier.issn 1756-8722
• dc.identifier.uri http://hdl.handle.net/10230/25723
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof Journal of Hematology & Oncology. 2015 Oct 24;8(1):119
• dc.rights © 2015 Rodriguez-Vida et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
• dc.subject.other Càncer -- Aspectes genèticsca
• dc.title Complexity of FGFR signalling in metastatic urothelial cancer.ca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca