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rdf:type |
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lifeskim:mentions |
umls-concept:C0025202,
umls-concept:C0044602,
umls-concept:C0100762,
umls-concept:C0127400,
umls-concept:C0140080,
umls-concept:C0243077,
umls-concept:C0285761,
umls-concept:C0439661,
umls-concept:C0683598,
umls-concept:C0752313,
umls-concept:C0812241,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1705325,
umls-concept:C1707719
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pubmed:issue |
6
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pubmed:dateCreated |
2010-12-15
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pubmed:abstractText |
BRAF is an attractive target for melanoma drug development. However, resistance to BRAF inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF inhibitors developed by chronic treatment of BRAF(V)???(E) melanoma cells with the BRAF inhibitor SB-590885; these cells are cross-resistant to other BRAF-selective inhibitors. Resistance involves flexible switching among the three RAF isoforms, underscoring the ability of melanoma cells to adapt to pharmacological challenges. IGF-1R/PI3K signaling was enhanced in resistant melanomas, and combined treatment with IGF-1R/PI3K and MEK inhibitors induced death of BRAF inhibitor-resistant cells. Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF-1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1878-3686
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pubmed:author |
pubmed-author:BrownKimberly DahlmanKD,
pubmed-author:CipollaAngela KAK,
pubmed-author:D'AndreaKurtK,
pubmed-author:Fukunaga-KalabisMizuhoM,
pubmed-author:GimottyPhyllis APA,
pubmed-author:HaydenJames EJE,
pubmed-author:HerlynMeenhardM,
pubmed-author:KeeDamienD,
pubmed-author:LaquerreSylvieS,
pubmed-author:LeeJohn TJT,
pubmed-author:LetreroRichardR,
pubmed-author:McArthurGrant AGA,
pubmed-author:NathansonKatherine LKL,
pubmed-author:PushparajanAnithaA,
pubmed-author:Santiago-WalkerAdemi EAE,
pubmed-author:SomasundaramRajasekharanR,
pubmed-author:SosmanJeffrey AJA,
pubmed-author:VillanuevaJessieJ,
pubmed-author:VulturAdinaA,
pubmed-author:WubbenhorstBradleyB,
pubmed-author:XuXiaoweiX
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
18
|
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pubmed:owner |
NLM
|
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pubmed:authorsComplete |
Y
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pubmed:pagination |
683-95
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pubmed:dateRevised |
2011-10-6
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pubmed:meshHeading |
pubmed-meshheading:21156289-Cell Line, Tumor,
pubmed-meshheading:21156289-Drug Resistance, Neoplasm,
pubmed-meshheading:21156289-Humans,
pubmed-meshheading:21156289-MAP Kinase Signaling System,
pubmed-meshheading:21156289-Melanoma,
pubmed-meshheading:21156289-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:21156289-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:21156289-Phosphorylation,
pubmed-meshheading:21156289-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:21156289-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:21156289-Receptor, IGF Type 1,
pubmed-meshheading:21156289-raf Kinases
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pubmed:year |
2010
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|
pubmed:articleTitle |
Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K.
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pubmed:affiliation |
The Wistar Institute, Philadelphia, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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