TY  - JOUR
AU  - Manzella, Gabriele
AU  - Schreck, Leonie D
AU  - Breunis, Willemijn B
AU  - Molenaar, Jan
AU  - Merks, Hans
AU  - Barr, Frederic G
AU  - Sun, Wenyue
AU  - Römmele, Michaela
AU  - Zhang, Luduo
AU  - Tchinda, Joelle
AU  - Ngo, Quy A
AU  - Bode, Peter
AU  - Delattre, Olivier
AU  - Surdez, Didier
AU  - Rekhi, Bharat
AU  - Niggli, Felix K
AU  - Schäfer, Beat W
AU  - Wachtel, Marco
TI  - Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity.
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-02246
SP  - 4629
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Antineoplastic Agents: pharmacology
KW  - Biological Specimen Banks
KW  - Drug Screening Assays, Antitumor: methods
KW  - Gene Expression Profiling
KW  - Humans
KW  - Phenotype
KW  - Protein Kinase Inhibitors
KW  - Proto-Oncogene Proteins c-akt: antagonists & inhibitors
KW  - Proto-Oncogene Proteins c-akt: genetics
KW  - Proto-Oncogene Proteins c-akt: metabolism
KW  - Rhabdomyosarcoma: drug therapy
KW  - Rhabdomyosarcoma: genetics
KW  - Rhabdomyosarcoma: metabolism
KW  - Tumor Cells, Cultured: drug effects
KW  - Xenograft Model Antitumor Assays
KW  - Antineoplastic Agents (NLM Chemicals)
KW  - Protein Kinase Inhibitors (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-akt (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32934208
C2  - pmc:PMC7492191
DO  - DOI:10.1038/s41467-020-18388-7
UR  - https://inrepo02.dkfz.de/record/294417
ER  -