Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma
Abstract Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation...
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Nature Portfolio
2021
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oai:doaj.org-article:e53c22a8e93b49a59453c658ede63a6d2021-12-02T17:51:26ZTargeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma10.1038/s41698-021-00220-02397-768Xhttps://doaj.org/article/e53c22a8e93b49a59453c658ede63a6d2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00220-0https://doaj.org/toc/2397-768XAbstract Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs.Michael BitzerStephan SpahnSepideh BabaeiMarius HorgerStephan SingerKlaus Schulze-OsthoffPavlos MissiosSergios GatidisDominik NannSven MatternVeit SchebleKonstantin NikolaouSorin Armeanu-EbingerMartin SchulzeChristopher SchroederSaskia BiskupJanina BehaManfred ClaassenKristina RuhmAntti PosoNisar P. MalekNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-7 (2021) |
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DOAJ |
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| topic |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Michael Bitzer Stephan Spahn Sepideh Babaei Marius Horger Stephan Singer Klaus Schulze-Osthoff Pavlos Missios Sergios Gatidis Dominik Nann Sven Mattern Veit Scheble Konstantin Nikolaou Sorin Armeanu-Ebinger Martin Schulze Christopher Schroeder Saskia Biskup Janina Beha Manfred Claassen Kristina Ruhm Antti Poso Nisar P. Malek Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma |
| description |
Abstract Intrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs. |
| format |
article |
| author |
Michael Bitzer Stephan Spahn Sepideh Babaei Marius Horger Stephan Singer Klaus Schulze-Osthoff Pavlos Missios Sergios Gatidis Dominik Nann Sven Mattern Veit Scheble Konstantin Nikolaou Sorin Armeanu-Ebinger Martin Schulze Christopher Schroeder Saskia Biskup Janina Beha Manfred Claassen Kristina Ruhm Antti Poso Nisar P. Malek |
| author_facet |
Michael Bitzer Stephan Spahn Sepideh Babaei Marius Horger Stephan Singer Klaus Schulze-Osthoff Pavlos Missios Sergios Gatidis Dominik Nann Sven Mattern Veit Scheble Konstantin Nikolaou Sorin Armeanu-Ebinger Martin Schulze Christopher Schroeder Saskia Biskup Janina Beha Manfred Claassen Kristina Ruhm Antti Poso Nisar P. Malek |
| author_sort |
Michael Bitzer |
| title |
Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma |
| title_short |
Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma |
| title_full |
Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma |
| title_fullStr |
Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma |
| title_full_unstemmed |
Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma |
| title_sort |
targeting extracellular and juxtamembrane fgfr2 mutations in chemotherapy-refractory cholangiocarcinoma |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/e53c22a8e93b49a59453c658ede63a6d |
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