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dc.contributor.authorFlørenes, Vivi Ann
dc.contributor.authorFlem-Karlsen, Karine
dc.contributor.authorMcFadden, Erin
dc.contributor.authorBergheim, Inger Riise
dc.contributor.authorNygaard, Vigdis
dc.contributor.authorNygård, Vegard Mokleiv
dc.contributor.authorFarstad, Inger Nina
dc.contributor.authorØy, Geir Frode
dc.contributor.authorEmilsen, Elisabeth
dc.contributor.authorFleten, Karianne Giller
dc.contributor.authorRee, Anne Hansen
dc.contributor.authorFlatmark, Kjersti
dc.contributor.authorGullestad, Hans Petter
dc.contributor.authorHermann, Robert
dc.contributor.authorRyder, Truls
dc.contributor.authorWernhoff, Patrik
dc.contributor.authorMælandsmo, Gunhild Mari
dc.date.accessioned2019-08-09T11:07:36Z
dc.date.available2019-08-09T11:07:36Z
dc.date.issued2019-05-13
dc.description.abstractAlthough clinical management of melanoma has changed considerably in recent years, intrinsic treatment resistance remains a severe problem and strategies to design personal treatment regimens are highly warranted. We have applied a three-dimensional (3D) <i>ex vivo</i> drug efficacy assay, exposing disaggregated cells from 38 freshly harvested melanoma lymph node metastases and 21 patient derived xenografts (PDXs) to clinical relevant drugs for 7 days, and examined its potential to evaluate therapy response. A strong association between Vemurafenib response and BRAF mutation status was achieved (<i>P</i> < .0001), while enhanced viability was seen in some NRAS mutated tumors. BRAF and NRAS mutated tumors responded comparably to the MEK inhibitor Cobimetinib. Based on the <i>ex vivo</i> results, two tumors diagnosed as BRAF wild-type by routine pathology examinations had to be re-evaluated; one was subsequently found to have a complex V600E mutation, the other a double BRAF mutation (V600E/K601 N). No BRAF inhibitor resistance mechanisms were identified, but PIK3CA and NF1 mutations were identified in two highly responsive tumors. Concordance between <i>ex vivo</i> drug responses using tissue from PDXs and corresponding patient tumors demonstrate that PDX models represent an indefinite source of tumor material that may allow <i>ex vivo</i> evaluation of numerous drugs and combinations, as well as studies of underlying molecular mechanisms. In conclusion, we have established a rapid and low cost <i>ex vivo</i> drug efficacy assay applicable on tumor tissue from patient biopsies. The 3D/spheroid format, limiting the influence from normal adjacent cells and allowing assessment of drug sensitivity to numerous drugs in one week, confirms its potential as a supplement to guide clinical decision, in particular in identifying non-responding patients.en_US
dc.description.sponsorshipSouth-Eastern Norway Regional Health Authority Cancer Society of Norwayen_US
dc.descriptionSource at <a href=https://doi.org/10.1016/j.tranon.2019.04.001>https://doi.org/10.1016/j.tranon.2019.04.001</a>.en_US
dc.identifier.citationFlørenes, V.A., Flem-Karlsen, K., McFadden, E., Bergheim, I.R., Nygaard, V., Nygård, V., ... Mælandsmo, G.M. (2019). A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases. <i>Translational Oncology, 12</i>(7), 951-958. https://doi.org/10.1016/j.tranon.2019.04.001en_US
dc.identifier.cristinIDFRIDAID 1708240
dc.identifier.doi10.1016/j.tranon.2019.04.001
dc.identifier.issn1936-5233
dc.identifier.urihttps://hdl.handle.net/10037/15891
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalTranslational Oncology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/BEHANDLING/218325/Norway/MetAction: Actionable Targets in Cancer Metastasis - from Bed to Bench to Byte to Bedside/MetAction/en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.titleA Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastasesen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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