Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma.

Reinartz, Roman; Wieland, Anja; Wang, Shanshan; Steindler, Dennis A; Rauschenbach, Laurèl; Reynolds, Brent A; Pincus, David W; Trageser, Daniel; Zheng, Tong; Kebir, Sied; Yachnis, Anthony; Simon, Matthias; Pietsch, Torsten; Cichon, Sven; Fimmers, Rolf; Brüstle, Oliver; Till, Andreas; Smith, Amy A; Silver, Daniel J; Glas, Martin; Schäfer, Niklas; Küpper, Marius; Scheffler, Björn; Shepherd, Timothy M; Liu, Ying; Hillmer, Axel M

doi:10.1158/1078-0432.CCR-15-2089

Items
Marc 21

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024	7	_	\|a 10.1158/1078-0432.CCR-15-2089 \|2 doi
024	7	_	\|a pmid:27521447 \|2 pmid
024	7	_	\|a pmc:PMC5241221 \|2 pmc
024	7	_	\|a 1078-0432 \|2 ISSN
024	7	_	\|a 1557-3265 \|2 ISSN
024	7	_	\|a altmetric:10474567 \|2 altmetric
037	_	_	\|a DZNE-2020-05358
041	_	_	\|a English
082	_	_	\|a 610
100	1	_	\|a Reinartz, Roman \|b 0
245	_	_	\|a Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma.
260	_	_	\|a Philadelphia, Pa. [u.a.] \|c 2017 \|b AACR
264	_	1	\|3 online \|2 Crossref \|b American Association for Cancer Research (AACR) \|c 2016-08-12
264	_	1	\|3 print \|2 Crossref \|b American Association for Cancer Research (AACR) \|c 2017-01-15
336	7	_	\|a article \|2 DRIVER
336	7	_	\|a Output Types/Journal article \|2 DataCite
336	7	_	\|a Journal Article \|b journal \|m journal \|0 PUB:(DE-HGF)16 \|s 1592212964_2127 \|2 PUB:(DE-HGF)
336	7	_	\|a ARTICLE \|2 BibTeX
336	7	_	\|a JOURNAL_ARTICLE \|2 ORCID
336	7	_	\|a Journal Article \|0 0 \|2 EndNote
520	_	_	\|a Investigation 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.
536	_	_	\|a 344 - Clinical and Health Care Research (POF3-344) \|0 G:(DE-HGF)POF3-344 \|c POF3-344 \|f POF III \|x 0
588	_	_	\|a Dataset connected to CrossRef, PubMed,
650	_	7	\|a Drug Combinations \|2 NLM Chemicals
650	_	2	\|a Animals \|2 MeSH
650	_	2	\|a Clonal Evolution: genetics \|2 MeSH
650	_	2	\|a Drug Combinations \|2 MeSH
650	_	2	\|a Drug Resistance, Neoplasm: genetics \|2 MeSH
650	_	2	\|a Genetic Heterogeneity \|2 MeSH
650	_	2	\|a Glioblastoma: drug therapy \|2 MeSH
650	_	2	\|a Glioblastoma: genetics \|2 MeSH
650	_	2	\|a Glioblastoma: pathology \|2 MeSH
650	_	2	\|a Humans \|2 MeSH
650	_	2	\|a Mice \|2 MeSH
650	_	2	\|a Xenograft Model Antitumor Assays \|2 MeSH
700	1	_	\|a Wang, Shanshan \|b 1
700	1	_	\|a Kebir, Sied \|b 2
700	1	_	\|a Silver, Daniel J \|b 3
700	1	_	\|a Wieland, Anja \|b 4
700	1	_	\|a Zheng, Tong \|b 5
700	1	_	\|a Küpper, Marius \|b 6
700	1	_	\|a Rauschenbach, Laurèl \|b 7
700	1	_	\|a Fimmers, Rolf \|0 P:(DE-HGF)0 \|b 8
700	1	_	\|a Shepherd, Timothy M \|b 9
700	1	_	\|a Trageser, Daniel \|b 10
700	1	_	\|a Till, Andreas \|b 11
700	1	_	\|a Schäfer, Niklas \|b 12
700	1	_	\|a Glas, Martin \|b 13
700	1	_	\|a Hillmer, Axel M \|b 14
700	1	_	\|a Cichon, Sven \|b 15
700	1	_	\|a Smith, Amy A \|b 16
700	1	_	\|a Pietsch, Torsten \|0 P:(DE-HGF)0 \|b 17
700	1	_	\|a Liu, Ying \|b 18
700	1	_	\|a Reynolds, Brent A \|b 19
700	1	_	\|a Yachnis, Anthony \|b 20
700	1	_	\|a Pincus, David W \|b 21
700	1	_	\|a Simon, Matthias \|b 22
700	1	_	\|a Brüstle, Oliver \|0 P:(DE-2719)9000037 \|b 23 \|u dzne
700	1	_	\|a Steindler, Dennis A \|b 24
700	1	_	\|a Scheffler, Björn \|0 P:(DE-HGF)0 \|b 25 \|e Corresponding author
773	1	8	\|a 10.1158/1078-0432.ccr-15-2089 \|b : American Association for Cancer Research (AACR), 2016-08-12 \|n 2 \|p 562-574 \|3 journal-article \|2 Crossref \|t Clinical Cancer Research \|v 23 \|y 2016 \|x 1078-0432
773	_	_	\|a 10.1158/1078-0432.CCR-15-2089 \|g Vol. 23, no. 2, p. 562 - 574 \|0 PERI:(DE-600)2036787-9 \|n 2 \|q 23:2<562 - 574 \|p 562-574 \|t Clinical cancer research \|v 23 \|y 2016 \|x 1078-0432
856	7	_	\|2 Pubmed Central \|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241221
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910	1	_	\|a Deutsches Zentrum für Neurodegenerative Erkrankungen \|0 I:(DE-588)1065079516 \|k DZNE \|b 23 \|6 P:(DE-2719)9000037
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914	1	_	\|y 2017
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Marc 21

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