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dc.contributor.author Pénzváltó Zsófia
dc.contributor.author Tegze Bálint
dc.contributor.author Szász Attila Marcell
dc.contributor.author Sztupinszki Zsófia
dc.contributor.author Likó István
dc.contributor.author Szendrői Attila
dc.contributor.author Schäfer R
dc.contributor.author Győrffy Balázs
dc.date.accessioned 2014-05-13T16:54:53Z
dc.date.available 2014-05-13T16:54:53Z
dc.date.issued 2013
dc.identifier.citation pagination=e59503; journalVolume=8; journalIssueNumber=3; journalTitle=PLOS ONE;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/63
dc.identifier.uri doi:10.1371/journal.pone.0059503
dc.description.abstract Because of the low overall response rates of 10-47% to targeted cancer therapeutics, there is an increasing need for predictive biomarkers. We aimed to identify genes predicting response to five already approved tyrosine kinase inhibitors. We tested 45 cancer cell lines for sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib at the clinically administered doses. A resistance matrix was determined, and gene expression profiles of the subsets of resistant vs. sensitive cell lines were compared. Triplicate gene expression signatures were obtained from the caArray project. Significance analysis of microarrays and rank products were applied for feature selection. Ninety-five genes were also measured by RT-PCR. In case of four sunitinib resistance associated genes, the results were validated in clinical samples by immunohistochemistry. A list of 63 top genes associated with resistance against the five tyrosine kinase inhibitors was identified. Quantitative RT-PCR analysis confirmed 45 of 63 genes identified by microarray analysis. Only two genes (ANXA3 and RAB25) were related to sensitivity against more than three inhibitors. The immunohistochemical analysis of sunitinib-treated metastatic renal cell carcinomas confirmed the correlation between RAB17, LGALS8, and EPCAM and overall survival. In summary, we determined predictive biomarkers for five tyrosine kinase inhibitors, and validated sunitinib resistance biomarkers by immunohistochemistry in an independent patient cohort. © 2013 Pénzváltó et al. hu
dc.relation.ispartof urn:issn:1932-6203
dc.title Identifying Resistance Mechanisms against Five Tyrosine Kinase Inhibitors Targeting the ERBB/RAS Pathway in 45 Cancer Cell Lines hu
dc.type Journal Article hu
dc.date.updated 2014-03-28T08:12:09Z
dc.language.rfc3066 en hu
dc.identifier.mtmt 2278388
dc.identifier.wos WOS:000317263900014
dc.identifier.pubmed 23555683
dc.contributor.department SE/ÁOK/K/ISZGYK/MTA-SE Gyermekgyógyászati és Nephrológiai Kutatócsoport
dc.contributor.department SE/ÁOK/K/I. Sz. Gyermekgyógyászati Klinika
dc.contributor.department SE/AOK/I/II. Sz. Patológiai Intézet
dc.contributor.department SE/AOK/K/Urológiai Klinika
dc.contributor.institution Semmelweis Egyetem


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