001     294417
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024 7 _ |a 10.1038/s41467-020-18388-7
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041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Manzella, Gabriele
|b 0
245 _ _ |a Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity.
260 _ _ |a [London]
|c 2020
|b Nature Publishing Group UK
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
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650 _ 7 |a Antineoplastic Agents
|2 NLM Chemicals
650 _ 7 |a Protein Kinase Inhibitors
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins c-akt
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Antineoplastic Agents: pharmacology
|2 MeSH
650 _ 2 |a Biological Specimen Banks
|2 MeSH
650 _ 2 |a Drug Screening Assays, Antitumor: methods
|2 MeSH
650 _ 2 |a Gene Expression Profiling
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Phenotype
|2 MeSH
650 _ 2 |a Protein Kinase Inhibitors
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins c-akt: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins c-akt: genetics
|2 MeSH
650 _ 2 |a Proto-Oncogene Proteins c-akt: metabolism
|2 MeSH
650 _ 2 |a Rhabdomyosarcoma: drug therapy
|2 MeSH
650 _ 2 |a Rhabdomyosarcoma: genetics
|2 MeSH
650 _ 2 |a Rhabdomyosarcoma: metabolism
|2 MeSH
650 _ 2 |a Tumor Cells, Cultured: drug effects
|2 MeSH
650 _ 2 |a Xenograft Model Antitumor Assays
|2 MeSH
700 1 _ |a Schreck, Leonie D
|b 1
700 1 _ |a Breunis, Willemijn B
|b 2
700 1 _ |a Molenaar, Jan
|b 3
700 1 _ |a Merks, Hans
|b 4
700 1 _ |a Barr, Frederic G
|b 5
700 1 _ |a Sun, Wenyue
|b 6
700 1 _ |a Römmele, Michaela
|b 7
700 1 _ |a Zhang, Luduo
|b 8
700 1 _ |a Tchinda, Joelle
|b 9
700 1 _ |a Ngo, Quy A
|b 10
700 1 _ |a Bode, Peter
|0 0000-0002-9633-4042
|b 11
700 1 _ |a Delattre, Olivier
|0 0000-0002-8730-2276
|b 12
700 1 _ |a Surdez, Didier
|0 0000-0002-7118-7859
|b 13
700 1 _ |a Rekhi, Bharat
|0 0000-0002-3509-4794
|b 14
700 1 _ |a Niggli, Felix K
|b 15
700 1 _ |a Schäfer, Beat W
|0 0000-0001-5988-2915
|b 16
700 1 _ |a Wachtel, Marco
|b 17
773 _ _ |a 10.1038/s41467-020-18388-7
|g Vol. 11, no. 1, p. 4629
|0 PERI:(DE-600)2553671-0
|n 1
|p 4629
|t Nature Communications
|v 11
|y 2020
|x 2041-1723
856 4 _ |u https://inrepo02.dkfz.de/record/294417/files/s41467-020-18388-7.pdf
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