DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kemper, Kristel | ko |
dc.contributor.author | Krijgsman, Oscar | ko |
dc.contributor.author | Kong, Xiangjun | ko |
dc.contributor.author | Cornelissen-Steijger, Paulien | ko |
dc.contributor.author | Shahrabi, Aida | ko |
dc.contributor.author | Weeber, Fleur | ko |
dc.contributor.author | van der Velden, Daphne L. | ko |
dc.contributor.author | Bleijerveld, Onno B. | ko |
dc.contributor.author | Kuilman, Thomas | ko |
dc.contributor.author | Kluin, Roel J. C. | ko |
dc.contributor.author | Sun, Chong | ko |
dc.contributor.author | Voest, Emile E. | ko |
dc.contributor.author | Ju, Young Seok | ko |
dc.contributor.author | Schumacher, Ton N. M. | ko |
dc.contributor.author | Altelaar, A. F. Maarten | ko |
dc.contributor.author | McDermott, Ultan | ko |
dc.contributor.author | Adams, David J. | ko |
dc.contributor.author | Blank, Christian U. | ko |
dc.contributor.author | Haanen, John B. | ko |
dc.contributor.author | Peeper, Daniel S. | ko |
dc.date.accessioned | 2017-01-18T02:55:46Z | - |
dc.date.available | 2017-01-18T02:55:46Z | - |
dc.date.created | 2017-01-04 | - |
dc.date.created | 2017-01-04 | - |
dc.date.created | 2017-01-04 | - |
dc.date.issued | 2016-06 | - |
dc.identifier.citation | CELL REPORTS, v.16, no.1, pp.263 - 277 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | http://hdl.handle.net/10203/219681 | - |
dc.description.abstract | The therapeutic landscape of melanoma is improving rapidly. Targeted inhibitors show promising results, but drug resistance often limits durable clinical responses. There is a need for in vivo systems that allow for mechanistic drug resistance studies and (combinatorial) treatment optimization. Therefore, we established a large collection of patient-derived xenografts (PDXs), derived from BRAF(V600E), NRAS(Q61), or BRAF(WT)/NRAS(WT) melanoma metastases prior to treatment with BRAF inhibitor and after resistance had occurred. Taking advantage of PDXs as a limitless source, we screened tumor lysates for resistance mechanisms. We identified a BRAF(V600E) protein harboring a kinase domain duplication (BRAF(V600E/DK)) in similar to 10% of the cases, both in PDXs and in an independent patient cohort. While BRAF(V600E/DK) depletion restored sensitivity to BRAF inhibition, a pan-RAF dimerization inhibitor effectively eliminated BRAF(V600E/DK)-expressing cells. These results illustrate the utility of this PDX platform and warrant clinical validation of BRAF dimerization inhibitors for this group of melanoma patients. | - |
dc.language | English | - |
dc.publisher | CELL PRESS | - |
dc.title | BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts | - |
dc.type | Article | - |
dc.identifier.wosid | 000378950700023 | - |
dc.identifier.scopusid | 2-s2.0-85008196691 | - |
dc.type.rims | ART | - |
dc.citation.volume | 16 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 263 | - |
dc.citation.endingpage | 277 | - |
dc.citation.publicationname | CELL REPORTS | - |
dc.identifier.doi | 10.1016/j.celrep.2016.05.064 | - |
dc.contributor.localauthor | Ju, Young Seok | - |
dc.contributor.nonIdAuthor | Kemper, Kristel | - |
dc.contributor.nonIdAuthor | Krijgsman, Oscar | - |
dc.contributor.nonIdAuthor | Kong, Xiangjun | - |
dc.contributor.nonIdAuthor | Cornelissen-Steijger, Paulien | - |
dc.contributor.nonIdAuthor | Shahrabi, Aida | - |
dc.contributor.nonIdAuthor | Weeber, Fleur | - |
dc.contributor.nonIdAuthor | van der Velden, Daphne L. | - |
dc.contributor.nonIdAuthor | Bleijerveld, Onno B. | - |
dc.contributor.nonIdAuthor | Kuilman, Thomas | - |
dc.contributor.nonIdAuthor | Kluin, Roel J. C. | - |
dc.contributor.nonIdAuthor | Sun, Chong | - |
dc.contributor.nonIdAuthor | Voest, Emile E. | - |
dc.contributor.nonIdAuthor | Schumacher, Ton N. M. | - |
dc.contributor.nonIdAuthor | Altelaar, A. F. Maarten | - |
dc.contributor.nonIdAuthor | McDermott, Ultan | - |
dc.contributor.nonIdAuthor | Adams, David J. | - |
dc.contributor.nonIdAuthor | Blank, Christian U. | - |
dc.contributor.nonIdAuthor | Haanen, John B. | - |
dc.contributor.nonIdAuthor | Peeper, Daniel S. | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | RAF INHIBITOR RESISTANCE | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | VEMURAFENIB RESISTANCE | - |
dc.subject.keywordPlus | METASTATIC MELANOMA | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | UP-REGULATION | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | CELL STATE | - |
dc.subject.keywordPlus | BRAF | - |
dc.subject.keywordPlus | ACTIVATION | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.