Journal Article

DKFZ-2024-02246

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity.

Manzella, G. ; Schreck, L. D. ; Breunis, W. B. ; Molenaar, J. ; Merks, H. ; Barr, F. G. ; Sun, W. ; Römmele, M. ; Zhang, L. ; Tchinda, J. ; Ngo, Q. A. ; Bode, P. ; Delattre, O. ; Surdez, D. ; Rekhi, B. ; Niggli, F. K. ; Schäfer, B. W. ; Wachtel, M.

2020
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-020-18388-7

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.

Keyword(s): Animals (MeSH) ; Antineoplastic Agents: pharmacology (MeSH) ; Biological Specimen Banks (MeSH) ; Drug Screening Assays, Antitumor: methods (MeSH) ; Gene Expression Profiling (MeSH) ; Humans (MeSH) ; Phenotype (MeSH) ; Protein Kinase Inhibitors (MeSH) ; Proto-Oncogene Proteins c-akt: antagonists & inhibitors (MeSH) ; Proto-Oncogene Proteins c-akt: genetics (MeSH) ; Proto-Oncogene Proteins c-akt: metabolism (MeSH) ; Rhabdomyosarcoma: drug therapy (MeSH) ; Rhabdomyosarcoma: genetics (MeSH) ; Rhabdomyosarcoma: metabolism (MeSH) ; Tumor Cells, Cultured: drug effects (MeSH) ; Xenograft Model Antitumor Assays (MeSH) ; Antineoplastic Agents ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins c-akt

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