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


Por: Kovar H, Amatruda J, Brunet E, Burdach S, Cidre-Aranaz F, de Alava E, Dirksen U, van der Ent W, Grohar P, Grünewald TG, Helman L, Houghton P, Iljin K, Korsching E, Ladanyi M, Lawlor E, Lessnick S, Ludwig J, Meltzer P, Metzler M, Mora J, Moriggl R, Nakamura T, Papamarkou T, Radic Sarikas B, Rédini F, Richter GH, Rossig C, Schadler K, Schäfer BW, Scotlandi K, Sheffield NC, Shelat A, Snaar-Jagalska E, Sorensen P, Stegmaier K, Stewart E, Sweet-Cordero A, Szuhai K, Tirado OM, Tirode F, Toretsky J, Tsafou K, Üren A, Zinovyev A and Delattre O

Publicada: 23 feb 2016
Categoría: Oncology

Resumen:
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Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies.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 intratumor 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and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits.

Filiaciones:
Kovar H:
 Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria

 Department of Pediatrics, Medical University Vienna, Vienna, Austria

Amatruda J:
 Departments of Pediatrics, Molecular Biology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

Brunet E:
 Museum National d'Histoire Naturelle, INSERM U1154, CNRS 7196, Paris, France

Burdach S:
 Children's Cancer Research Center and Department of Pediatrics, Klinikum rechts der Isar, Technical University and Comprehensive Cancer Center Munich (CCCM), Munich, Germany

Cidre-Aranaz F:
 Unidad de Tumores Sólidos Infantiles, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain

de Alava E:
 Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital /CSIC/University de Sevilla, Department of Pathology, Seville, Spain

Dirksen U:
 University Children´s Hospital Muenster, Pediatric Hematology and Oncology, Muenster, Germany

van der Ent W:
 INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France

 Institute of Biology, Leiden University, Leiden, The Netherlands

Grohar P:
 Van Andel Institute, Center for Cancer and Cell Biology and Helen DeVos Children's Hospital, Grand Rapids, MI, USA

Grünewald TG:
 Laboratory for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, Munich, Germany

Helman L:
 Center for Cancer Rearch, NCI, NIH, Bethesda, MA, USA

Houghton P:
 Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA

Iljin K:
 VTT Technical Research Centre of Finland Ltd, Espoo, Finland

Korsching E:
 Institute of Bioinformatics, Faculty of Medicine, University of Muenster, Muenster, Germany

Ladanyi M:
 Department of Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Lawlor E:
 Department of Pediatrics and Department of Pathology, University of Michigan, Ann Arbor, MI, USA

Lessnick S:
 Center for Childhood Cancer and Blood Disorders, Nationwide Children's Hospital, and the Division of Pediatric Hematology/Oncology/BMT, The Ohio State University, Columbus, OH, USA

Ludwig J:
 Department of Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA

Meltzer P:
 Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

Metzler M:
 Pediatric Oncology and Hematology, University Hospital Erlangen, Erlangen, Germany

Mora J:
 Department of Pediatric Oncology, Sant Joan de Déu Hospital, Barcelona, Spain

Moriggl R:
 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria

 Institute of Animal Breeding and Genetics, University of Veterinary Medicine and Medical University, Vienna, Austria

Nakamura T:
 Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

Papamarkou T:
 University of Glasgow, School of Mathematics and Statistics, Glasgow, UK

Radic Sarikas B:
 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

Rédini F:
 INSERM UMR957, Université de Nantes, Nantes, France

Richter GH:
 Children's Cancer Research Center and Department of Pediatrics, Klinikum rechts der Isar, Technical University and Comprehensive Cancer Center Munich (CCCM), Munich, Germany

Rossig C:
 University Children´s Hospital Muenster, Pediatric Hematology and Oncology, Muenster, Germany

Schadler K:
 Department of Pediatrics Research, MD Anderson Cancer Center, Houston, TX, USA

Schäfer BW:
 Department of Oncology and Children's Research Center, University Children's Hospital, Zurich, Switzerland

Scotlandi K:
 CRS Development of Biomolecular Therapies, Experimental Oncology Lab, Rizzoli Institute, Bologna, Italy

Sheffield NC:
 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

Shelat A:
 Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis,TN, USA

Snaar-Jagalska E:
 Institute of Biology, Leiden University, Leiden, The Netherlands

Sorensen P:
 Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada

Stegmaier K:
 Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA

Stewart E:
 Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA

Sweet-Cordero A:
 Division of Hematology and Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA

Szuhai K:
 Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

Tirado OM:
 Sarcoma Research Group, Molecular Oncology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain

Tirode F:
 INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France

Toretsky J:
 Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA

Tsafou K:
 Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA

Üren A:
 Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA

Zinovyev A:
 INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France

 INSERM, U900, Paris, France

 Ecole des Mines ParisTech, Fontainbleau, France

Delattre O:
 INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France
ISSN: 19492553





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Tipo de documento: Article
Volumen: 7 Número: 8
Páginas: 8613-8624
WOS Id: 000375618100014
ID de PubMed: 26802024
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