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@ARTICLE{Reinartz:139036,
author = {Reinartz, Roman and Wang, Shanshan and Kebir, Sied and
Silver, Daniel J and Wieland, Anja and Zheng, Tong and
Küpper, Marius and Rauschenbach, Laurèl and Fimmers, Rolf
and Shepherd, Timothy M and Trageser, Daniel and Till,
Andreas and Schäfer, Niklas and Glas, Martin and Hillmer,
Axel M and Cichon, Sven and Smith, Amy A and Pietsch,
Torsten and Liu, Ying and Reynolds, Brent A and Yachnis,
Anthony and Pincus, David W and Simon, Matthias and
Brüstle, Oliver and Steindler, Dennis A and Scheffler,
Björn},
title = {{F}unctional {S}ubclone {P}rofiling for {P}rediction of
{T}reatment-{I}nduced {I}ntratumor {P}opulation {S}hifts and
{D}iscovery of {R}ational {D}rug {C}ombinations in {H}uman
{G}lioblastoma.},
journal = {Clinical cancer research},
volume = {23},
number = {2},
issn = {1078-0432},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DZNE-2020-05358},
pages = {562-574},
year = {2017},
abstract = {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.},
keywords = {Animals / Clonal Evolution: genetics / Drug Combinations /
Drug Resistance, Neoplasm: genetics / Genetic Heterogeneity
/ Glioblastoma: drug therapy / Glioblastoma: genetics /
Glioblastoma: pathology / Humans / Mice / Xenograft Model
Antitumor Assays / Drug Combinations (NLM Chemicals)},
cin = {Cell Programming Unit},
ddc = {610},
cid = {I:(DE-2719)1013013},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27521447},
pmc = {pmc:PMC5241221},
doi = {10.1158/1078-0432.CCR-15-2089},
url = {https://pub.dzne.de/record/139036},
}