Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity

Gabriele Manzella, Leonie D Schreck, Willemijn B Breunis, Jan Molenaar, Hans Merks, Frederic G Barr, Wenyue Sun, Michaela Römmele, Luduo Zhang, Joelle Tchinda, Quy A Ngo, Peter Bode, Olivier Delattre, Didier Surdez, Bharat Rekhi, Felix K Niggli, Beat W Schäfer, Marco Wachtel

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

14 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Artikelnummer4629
Pagina's (van-tot)4629
TijdschriftNature communications
Volume11
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 15 sep. 2020

Vingerafdruk

Duik in de onderzoeksthema's van 'Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity'. Samen vormen ze een unieke vingerafdruk.

Citeer dit