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dc.contributor.authorKarlsen, Karine Flem
dc.contributor.authorMcFadden, Erin
dc.contributor.authorOmar, Nasrin
dc.contributor.authorHaugen, Mads Haugland
dc.contributor.authorØy, Geir Frode
dc.contributor.authorRyder, Truls
dc.contributor.authorGullestad, Hans Petter
dc.contributor.authorHermann, Robert
dc.contributor.authorMælandsmo, Gunhild Mari
dc.contributor.authorFlørenes, Vivi Ann
dc.date.accessioned2020-02-06T11:34:05Z
dc.date.available2020-02-06T11:34:05Z
dc.date.embargoEndDate2020-12-26
dc.date.issued2019-12-23
dc.description.abstractReceptor tyrosine kinase AXL is found upregulated in various types of cancer, including melanoma, and correlates with an aggressive cancer phenotype, inducing cell proliferation and epithelial-to-mesenchymal transition. Additionally, AXL has recently been linked to chemotherapy resistance and inhibition of AXL is found to increase DNA damage and reduce expression of DNA repair proteins. In light of this, we aimed to investigate if targeting AXL together with DNA damage response proteins would be therapeutically beneficial. Using melanoma cell lines, we observed that combined reduction of AXL and CHK1/CHK2 signaling decreased proliferation, deregulated cell cycle progression, increased apoptosis and reduced expression of DNA damage response proteins. Enhanced therapeutic effect of combined- as compared to mono-treatments was further observed in a patient-derived xenograft model and, of particular interest, when applying a three-dimensional ex vivo spheroid drug-sensitivity assay on tumor cells harvested directly from 27 patients with melanoma lymph node metastases. Together, these results indicate that targeting AXL together with the DNA damage response pathway could be a promising treatment strategy in melanoma and that further investigations in patient groups lacking treatment alternatives should be pursued.en_US
dc.identifier.citationKarlsen, McFadden E, Omar, Haugen MH, Øy GF, Ryder T, Gullestad HP, Hermann R, Mælandsmo GM, Flørenes VA. Targeting AXL and the DNA damage response pathway as a novel therapeutic strategy in melanoma. Molecular Cancer Therapeutics. 2019en_US
dc.identifier.cristinIDFRIDAID 1780976
dc.identifier.doi10.1158/1535-7163.MCT-19-0290
dc.identifier.issn1535-7163
dc.identifier.issn1538-8514
dc.identifier.urihttps://hdl.handle.net/10037/17338
dc.language.isoengen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.relation.journalMolecular Cancer Therapeutics
dc.rights.accessRightsembargoedAccessen_US
dc.rights.holderCopyright ©2019, American Association for Cancer Research.en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleTargeting AXL and the DNA damage response pathway as a novel therapeutic strategy in melanomaen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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