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Article Dans Une Revue Oncotarget Année : 2016

The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease

1 Children’s Cancer Research Institute [Vienna, Austria]
2 Department of Pediatrics [Vienna, Austria]
3 Departments of Pediatrics, Molecular Biology and Internal Medicine [Dallas, TX, USA]
4 STRING - Structure et Instabilité des Génomes
5 MRI TUM - Klinikum rechts der Isar
6 Unidad de Tumores Sólidos Infantiles – Unidad de Investigación Biomédica [Madrid, Spain]
7 USAL-CSIC - Laboratorio de Patología Molecular
8 Universitätsklinikum Münster [Munster, Germany]
9 U830 - Unité de génétique et biologie des cancers
10 Institute of Biology [Leiden, The Netherlands]
11 Center for Cancer and Cell Biology [Grand Rapids, MI, USA]
12 Laboratory for Pediatric Sarcoma Biology [Munich, Germany]
13 Center for Cancer Rearch [Bethesda, MA, USA]
14 Greehey Children’s Cancer Research Institute [San Antonio, TX, USA]
15 VTT - VTT Technical Research Centre of Finland
16 Institute of Bioinformatics [Muenster, Germany]
17 Department of Pathology and Human Oncology and Pathogenesis Program [New York, NY, USA]
18 Department of Pediatrics and Department of Pathology [Ann Arbor, MI, USA]
19 Division of Pediatric Hematology/ Oncology/BMT [Columbus, OH, USA]
20 Department of Sarcoma Medical Oncology [Houston, TX, USA]
21 Center for Cancer Research - Genetics Branch [Bethesda, MD, USA]
22 Pediatric Oncology and Hematology [Erlangen, Germany]
23 Department of Pediatric Oncology [Barcelona, Spain]
24 Ludwig Boltzmann Institute for Cancer Research [Vienna, Austria]
25 Department for Biomedical Sciences - Institute of Animal Breeding and Genetics [Vienna, Austria]
26 Division of Carcinogenesis [Tokyo, Japan]
27 School of Mathematics and Statistics [Glasgow, UK]
28 CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences [Vienna, Austria]
29 PhAN - Physiopathologie des Adaptations Nutritionnelles
30 Department of Pediatrics Research [Houston, TX, USA]
31 UZH - Universität Zürich [Zürich] = University of Zurich
32 Experimental Oncology Lab - CRS Development of Biomolecular Therapies [Bologna, Italy]
33 Department of Chemical Biology and Therapeutics [Memphis,TN, USA]
34 Department of Molecular Oncology [British Columbia, Canada]
35 Department of Pediatric Oncology [Boston, MA, USA]
36 Department of Developmental Neurobiology [Memphis, TN, USA]
37 Department of Pediatrics - Division of Hematology and Oncology [Stanford, CA, USA]
38 Department of Molecular Cell Biology [Leiden, The Netherlands]
39 Sarcoma Research Group - Molecular Oncology Laboratory [Barcelona, Spain]
40 Department of Oncology [Washington, DC, USA]
41 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
Erika Brunet
Franck Tirode

Résumé

Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second "European interdisciplinary Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNA-sequencing of recently described Ewing-like sarcomas with variant translocations identified them as biologically distinct diseases. Various presentations adressed mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were presented shedding light on the molecular underpinnings of genetic permissiveness to this disease uncovering interaction of EWS-FLI1 with recently discovered susceptibility loci. Epigenetic context as a consequence of the interaction between the oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as dominant theme in the discussion of the molecular pathogenesis and inter- and intra-tumor heterogeneity of Ewing sarcoma, and the difficulty to generate animal models faithfully recapitulating the human disease. The problem of preclinical development of biologically targeted therapeutics was discussed and promising perspectives were offered from the study of novel in vitro models. Finally, it was concluded that in order to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits.
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Dates et versions

inserm-01703282 , version 1 (07-02-2018)

Identifiants

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Heinrich Kovar, James Amatruda, Erika Brunet, Stefan Burdach, Florencia Cidre-Aranaz, et al.. The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease. Oncotarget, 2016, 7 (8), pp.8613-24. ⟨10.18632/oncotarget.6937⟩. ⟨inserm-01703282⟩
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