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Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-228
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dc.contributor.authorRusso, Alexandra-
dc.contributor.authorParet, Claudia-
dc.contributor.authorAlt, Francesca-
dc.contributor.authorBurhenne, Jürgen-
dc.contributor.authorFresnais, Margaux-
dc.contributor.authorWagner, Wolfgang-
dc.contributor.authorGlaser, Martin-
dc.contributor.authorBender, Hannah-
dc.contributor.authorHuprich, Sabrina-
dc.contributor.authorHarter, Patrick N.-
dc.contributor.authorFilipski, Katharina-
dc.contributor.authorLehmann, Nadine-
dc.contributor.authorBackes, Nora-
dc.contributor.authorRoth, Lea-
dc.contributor.authorSeidmann, Larissa-
dc.contributor.authorSommer, Clemens-
dc.contributor.authorBrockmann, Marc-
dc.contributor.authorPietsch, Torsten-
dc.contributor.authorNeu, A. Marie-
dc.contributor.authorWingerter, Arthur-
dc.contributor.authorFaber, Jörg-
dc.date.accessioned2019-11-11T13:22:10Z-
dc.date.available2019-11-11T14:22:10Z-
dc.date.issued2019-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/230-
dc.description.abstractThe insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin-
dc.language.isoeng-
dc.rightsCC BYde_DE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleCeritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumoren_GB
dc.typeZeitschriftenaufsatzde_DE
dc.identifier.urnurn:nbn:de:hebis:77-publ-594122-
dc.identifier.doihttp://doi.org/10.25358/openscience-228-
jgu.type.dinitypearticle-
jgu.type.versionPublished versionen_GB
jgu.type.resourceText-
jgu.organisation.departmentFB 04 Medizin-
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleInternational journal of molecular sciences-
jgu.journal.volume20-
jgu.journal.issue17-
jgu.pages.alternativeArt. 4267-
jgu.publisher.year2019-
jgu.publisher.nameMolecular Diversity Preservation International-
jgu.publisher.placeBasel-
jgu.publisher.urihttp://dx.doi.org/10.3390/ijms20174267-
jgu.publisher.issn1422-0067-
jgu.publisher.issn1661-6596-
jgu.organisation.placeMainz-
jgu.subject.ddccode610-
opus.date.accessioned2019-11-11T13:22:10Z-
opus.date.modified2020-03-16T11:31:28Z-
opus.date.available2019-11-11T14:22:10-
opus.subject.dfgcode00-000-
opus.organisation.stringFB 04: Medizin: Institut für Neuroradiologiede_DE
opus.organisation.stringFB 04: Medizin: Institut für Pathologiede_DE
opus.organisation.stringFB 04: Medizin: Zentrum für Kinder- und Jugendmedizinde_DE
opus.organisation.stringFB 04: Medizin: Klinik und Poliklinik für Neurochirurgiede_DE
opus.organisation.stringFB 04: Medizin: Institut für Neuropathologiede_DE
opus.organisation.stringFB 04: Medizin: Universitäres Centrum für Tumorerkrankungen (UCT) Mainzde_DE
opus.identifier.opusid59412-
opus.institute.number0421-
opus.institute.number0423-
opus.institute.number0462-
opus.institute.number0471-
opus.institute.number0481-
opus.institute.number0483-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_GB
opus.affiliatedRusso, Alexandra-
opus.affiliatedParet, Claudia-
opus.affiliatedAlt, Francesca-
opus.affiliatedWagner, Wolfgang-
opus.affiliatedGlaser, Martin-
opus.affiliatedLehmann, Nadine-
opus.affiliatedBackes, Nora-
opus.affiliatedRoth, Lea-
opus.affiliatedSeidmann, Larissa-
opus.affiliatedSommer, Clemens-
opus.affiliatedBrockmann, Marc-
opus.affiliatedWingerter, Arthur-
opus.affiliatedFaber, Jörg-
jgu.publisher.doi10.3390/ijms20174267
jgu.organisation.rorhttps://ror.org/023b0x485
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