Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2020

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

(1) , (1) , (1, 2) , (2) , (2) , (3) , (3) , (1) , (1) , (1) , (1) , (4) , (5) , (5) , (6) , (1) , (1) , (1)
1
2
3
4
5
6

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.
Fichier principal
Vignette du fichier
s41467-020-18388-7.pdf (2.94 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

inserm-02958175 , version 1 (05-10-2020)

Identifiers

Cite

Gabriele Manzella, Leonie D Schreck, Willemijn B Breunis, Jan Molenaar, Hans Merks, et al.. Phenotypic profiling with a living biobank of primary rhabdomyosarcoma unravels disease heterogeneity and AKT sensitivity. Nature Communications, 2020, 11 (1), pp.4629. ⟨10.1038/s41467-020-18388-7⟩. ⟨inserm-02958175⟩
105 View
50 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More