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@ARTICLE{Manzella:294417,
author = {G. Manzella and L. D. Schreck and W. B. Breunis and J.
Molenaar and H. Merks and F. G. Barr and W. Sun and M.
Römmele and L. Zhang and J. Tchinda and Q. A. Ngo and P.
Bode and O. Delattre and D. Surdez and B. Rekhi and F. K.
Niggli and B. W. Schäfer and M. Wachtel},
title = {{P}henotypic profiling with a living biobank of primary
rhabdomyosarcoma unravels disease heterogeneity and {AKT}
sensitivity.},
journal = {Nature Communications},
volume = {11},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-02246},
pages = {4629},
year = {2020},
abstract = {Cancer therapy is currently shifting from broadly used
cytotoxic drugs to patient-specific precision therapies.
Druggable driver oncogenes, identified by molecular
analyses, are present in only a subset of patients.
Functional profiling of primary tumor cells could circumvent
these limitations, but suitable platforms are unavailable
for most cancer entities. Here, we describe an in vitro drug
profiling platform for rhabdomyosarcoma (RMS), using a
living biobank composed of twenty RMS patient-derived
xenografts (PDX) for high-throughput drug testing. Optimized
in vitro conditions preserve phenotypic and molecular
characteristics of primary PDX cells and are compatible with
propagation of cells directly isolated from patient tumors.
Besides a heterogeneous spectrum of responses of largely
patient-specific vulnerabilities, profiling with a large
drug library reveals a strong sensitivity towards AKT
inhibitors in a subgroup of RMS. Overall, our study
highlights the feasibility of in vitro drug profiling of
primary RMS for patient-specific treatment selection in a
co-clinical setting.},
keywords = {Animals / Antineoplastic Agents: pharmacology / Biological
Specimen Banks / Drug Screening Assays, Antitumor: methods /
Gene Expression Profiling / Humans / Phenotype / Protein
Kinase Inhibitors / Proto-Oncogene Proteins c-akt:
antagonists $\&$ inhibitors / Proto-Oncogene Proteins c-akt:
genetics / Proto-Oncogene Proteins c-akt: metabolism /
Rhabdomyosarcoma: drug therapy / Rhabdomyosarcoma: genetics
/ Rhabdomyosarcoma: metabolism / Tumor Cells, Cultured: drug
effects / Xenograft Model Antitumor Assays / Antineoplastic
Agents (NLM Chemicals) / Protein Kinase Inhibitors (NLM
Chemicals) / Proto-Oncogene Proteins c-akt (NLM Chemicals)},
ddc = {500},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32934208},
pmc = {pmc:PMC7492191},
doi = {10.1038/s41467-020-18388-7},
url = {https://inrepo02.dkfz.de/record/294417},
}