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000139036 0247_ $$2doi$$a10.1158/1078-0432.CCR-15-2089
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000139036 0247_ $$2pmc$$apmc:PMC5241221
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000139036 0247_ $$2ISSN$$a1557-3265
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000139036 041__ $$aEnglish
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000139036 1001_ $$aReinartz, Roman$$b0
000139036 245__ $$aFunctional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma.
000139036 260__ $$aPhiladelphia, Pa. [u.a.]$$bAACR$$c2017
000139036 264_1 $$2Crossref$$3online$$bAmerican Association for Cancer Research (AACR)$$c2016-08-12
000139036 264_1 $$2Crossref$$3print$$bAmerican Association for Cancer Research (AACR)$$c2017-01-15
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000139036 520__ $$aInvestigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors.Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and interindividual spectra of drug resistance profiles in vitro In a personalized setting, we explored whether differences in pharmacologic sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors.Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential antiglioblastoma compounds. A more comprehensive intratumoral analysis revealed that stable genetic and phenotypic characteristics of coexisting subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacologic profiles could be shown for establishing rational strategies for individualized secondary lines of treatment.Our data provide a previously unrecognized strategy for revealing functional consequences of intratumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. Clin Cancer Res; 23(2); 562-74. ©2016 AACR.
000139036 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
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000139036 650_7 $$2NLM Chemicals$$aDrug Combinations
000139036 650_2 $$2MeSH$$aAnimals
000139036 650_2 $$2MeSH$$aClonal Evolution: genetics
000139036 650_2 $$2MeSH$$aDrug Combinations
000139036 650_2 $$2MeSH$$aDrug Resistance, Neoplasm: genetics
000139036 650_2 $$2MeSH$$aGenetic Heterogeneity
000139036 650_2 $$2MeSH$$aGlioblastoma: drug therapy
000139036 650_2 $$2MeSH$$aGlioblastoma: genetics
000139036 650_2 $$2MeSH$$aGlioblastoma: pathology
000139036 650_2 $$2MeSH$$aHumans
000139036 650_2 $$2MeSH$$aMice
000139036 650_2 $$2MeSH$$aXenograft Model Antitumor Assays
000139036 7001_ $$aWang, Shanshan$$b1
000139036 7001_ $$aKebir, Sied$$b2
000139036 7001_ $$aSilver, Daniel J$$b3
000139036 7001_ $$aWieland, Anja$$b4
000139036 7001_ $$aZheng, Tong$$b5
000139036 7001_ $$aKüpper, Marius$$b6
000139036 7001_ $$aRauschenbach, Laurèl$$b7
000139036 7001_ $$0P:(DE-HGF)0$$aFimmers, Rolf$$b8
000139036 7001_ $$aShepherd, Timothy M$$b9
000139036 7001_ $$aTrageser, Daniel$$b10
000139036 7001_ $$aTill, Andreas$$b11
000139036 7001_ $$aSchäfer, Niklas$$b12
000139036 7001_ $$aGlas, Martin$$b13
000139036 7001_ $$aHillmer, Axel M$$b14
000139036 7001_ $$aCichon, Sven$$b15
000139036 7001_ $$aSmith, Amy A$$b16
000139036 7001_ $$0P:(DE-HGF)0$$aPietsch, Torsten$$b17
000139036 7001_ $$aLiu, Ying$$b18
000139036 7001_ $$aReynolds, Brent A$$b19
000139036 7001_ $$aYachnis, Anthony$$b20
000139036 7001_ $$aPincus, David W$$b21
000139036 7001_ $$aSimon, Matthias$$b22
000139036 7001_ $$0P:(DE-2719)9000037$$aBrüstle, Oliver$$b23$$udzne
000139036 7001_ $$aSteindler, Dennis A$$b24
000139036 7001_ $$0P:(DE-HGF)0$$aScheffler, Björn$$b25$$eCorresponding author
000139036 77318 $$2Crossref$$3journal-article$$a10.1158/1078-0432.ccr-15-2089$$b : American Association for Cancer Research (AACR), 2016-08-12$$n2$$p562-574$$tClinical Cancer Research$$v23$$x1078-0432$$y2016
000139036 773__ $$0PERI:(DE-600)2036787-9$$a10.1158/1078-0432.CCR-15-2089$$gVol. 23, no. 2, p. 562 - 574$$n2$$p562-574$$q23:2<562 - 574$$tClinical cancer research$$v23$$x1078-0432$$y2016
000139036 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241221
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