1. Fusion-negative Rhabdomyosarcoma 3D-organoids as an innovative model to predict resistance to cell death inducers
- Author
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Clara Savary, Paul Huchedé, Léa Luciana, Arthur Tourbez, Clémence Deligne, Cécile Picard, Thomas Diot, Claire Coquet, Nina Meynard, Marion Le Grand, Laurie Tonon, Nicolas Gadot, Cyril Degletagne, Sophie Léon, Valéry Attignon, Alexandra Bomane, Isabelle Rochet, Kevin Müller, Virginie Mournetas, Christophe Bergeron, Paul Rinaudo, Aurélie Dutour, Martine Cordier-Bussat, Frédérique Dijoud, Nadège Corradini, Delphine Maucort-Boulch, Eddy Pasquier, Jean-Yves Blay, Marie Castets, Laura Broutier, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], ADLIN Science, Pasquier, Eddy, and Service de Biostatistiques [Lyon]
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] - Abstract
Rhabdomyosarcoma (RMS) is the main form of soft-tissue sarcoma in children and adolescents. For 20 years, and despite international clinical trials, its cure rate has not really improved, and remains stuck at 20% in case of relapse. The definition of new effective therapeutic combinations is hampered by the lack of reliable models, which complicate the transposition of promising results obtained in pre-clinical studies into efficient solutions for young patients. Inter-patient heterogeneity, particularly in the so-called fusion-negative group (FNRMS), adds an additional level of difficulty in optimizing the clinical management of children and adolescents with RMS.Here, we describe an original 3D-organoid model derived from relapsed FNRMS and show that it finely mimics the characteristics of the original tumor, including inter- and intra-tumoral heterogeneity. Moreover, we have established the proof-of-concept of their preclinical potential by re-evaluating the therapeutic opportunities of targeting apoptosis in FNRMS from a streamlined approach based on the exploitation of bulk and single-cell omics data.
- Published
- 2022