Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor

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, Marie A.
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.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.identifier.doihttp://doi.org/10.25358/openscience-228
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/230
dc.identifier.urnurn:nbn:de:hebis:77-publ-594122
dc.language.isoeng
dc.rightsCC-BY-4.0de_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
jgu.journal.issue17
jgu.journal.titleInternational journal of molecular sciences
jgu.journal.volume20
jgu.organisation.departmentFB 04 Medizin
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number2700
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.alternativeArt. 4267
jgu.publisher.doi10.3390/ijms20174267
jgu.publisher.issn1422-0067
jgu.publisher.issn1661-6596
jgu.publisher.nameMolecular Diversity Preservation International
jgu.publisher.placeBasel
jgu.publisher.urihttp://dx.doi.org/10.3390/ijms20174267
jgu.publisher.year2019
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode610
jgu.type.dinitypeArticle
jgu.type.resourceText
jgu.type.versionPublished versionen_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
opus.date.accessioned2019-11-11T13:22:10Z
opus.date.available2019-11-11T14:22:10
opus.date.modified2020-03-16T11:31:28Z
opus.identifier.opusid59412
opus.institute.number0421
opus.institute.number0423
opus.institute.number0462
opus.institute.number0471
opus.institute.number0481
opus.institute.number0483
opus.metadataonlyfalse
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.subject.dfgcode00-000
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_GB

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