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dc.contributor.authorMannsåker, Trond Are
dc.contributor.authorHoang, Tuyen
dc.contributor.authorAasen, Synnøve Nymark
dc.contributor.authorBjørnstad, Ole Vidhammer
dc.contributor.authorParajuli, Himalaya
dc.contributor.authorSundstrøm, Terje
dc.contributor.authorThorsen, Frits
dc.date.accessioned2021-11-30T09:15:22Z
dc.date.available2021-11-30T09:15:22Z
dc.date.created2021-11-26T22:45:57Z
dc.date.issued2021-11-14
dc.identifier.issn1422-0067
dc.identifier.urihttps://hdl.handle.net/11250/2832023
dc.description.abstractMelanomas have a high potential to metastasize to the brain. Recent advances in targeted therapies and immunotherapies have changed the therapeutical landscape of extracranial melanomas. However, few patients with melanoma brain metastasis (MBM) respond effectively to these treatments and new therapeutic strategies are needed. Cabozantinib is a receptor tyrosine kinase (RTK) inhibitor, already approved for the treatment of non-skin-related cancers. The drug targets several of the proteins that are known to be dysregulated in melanomas. The anti-tumor activity of cabozantinib was investigated using three human MBM cell lines. Cabozantinib treatment decreased the viability of all cell lines both when grown in monolayer cultures and as tumor spheroids. The in vitro cell migration was also inhibited and apoptosis was induced by cabozantinib. The phosphorylated RTKs p-PDGF-Rα, p-IGF-1R, p-MERTK and p-DDR1 were found to be downregulated in the p-RTK array of the MBM cells after cabozantinib treatment. Western blot validated these results and showed that cabozantinib treatment inhibited p-Akt and p-MEK 1/2. Further investigations are warranted to elucidate the therapeutic potential of cabozantinib for patients with MBM.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleCabozantinib is effective in melanoma brain metastasis cell lines and affects key signaling pathwaysen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 the authorsen_US
dc.source.articlenumber12296en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/ijms222212296
dc.identifier.cristin1960073
dc.source.journalInternational Journal of Molecular Sciencesen_US
dc.identifier.citationInternational Journal of Molecular Sciences. 2021, 22 (22), 12296.en_US
dc.source.volume22en_US
dc.source.issue22en_US


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