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Oncotarget. 2016 Feb 23;7(8):8613-24. doi: 10.18632/oncotarget.6937.

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

Author information

1
Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria.
2
Department of Pediatrics, Medical University Vienna, Vienna, Austria.
3
Departments of Pediatrics, Molecular Biology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
4
Museum National d'Histoire Naturelle, INSERM U1154, CNRS 7196, Paris, France.
5
Children's Cancer Research Center and Department of Pediatrics, Klinikum rechts der Isar, Technical University and Comprehensive Cancer Center Munich (CCCM), Munich, Germany.
6
Unidad de Tumores Sólidos Infantiles, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain.
7
Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital /CSIC/University de Sevilla, Department of Pathology, Seville, Spain.
8
University Children´s Hospital Muenster, Pediatric Hematology and Oncology, Muenster, Germany.
9
INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
10
Institute of Biology, Leiden University, Leiden, The Netherlands.
11
Van Andel Institute, Center for Cancer and Cell Biology and Helen DeVos Children's Hospital, Grand Rapids, MI, USA.
12
Laboratory for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, Munich, Germany.
13
Center for Cancer Rearch, NCI, NIH, Bethesda, MA, USA.
14
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA.
15
VTT Technical Research Centre of Finland Ltd, Espoo, Finland.
16
Institute of Bioinformatics, Faculty of Medicine, University of Muenster, Muenster, Germany.
17
Department of Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
18
Department of Pediatrics and Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
19
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.
20
Department of Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
21
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
22
Pediatric Oncology and Hematology, University Hospital Erlangen, Erlangen, Germany.
23
Department of Pediatric Oncology, Sant Joan de Déu Hospital, Barcelona, Spain.
24
Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.
25
Institute of Animal Breeding and Genetics, University of Veterinary Medicine and Medical University, Vienna, Austria.
26
Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
27
University of Glasgow, School of Mathematics and Statistics, Glasgow, UK.
28
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
29
INSERM UMR957, Université de Nantes, Nantes, France.
30
Department of Pediatrics Research, MD Anderson Cancer Center, Houston, TX, USA.
31
Department of Oncology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
32
CRS Development of Biomolecular Therapies, Experimental Oncology Lab, Rizzoli Institute, Bologna, Italy.
33
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis,TN, USA.
34
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
35
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
36
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
37
Division of Hematology and Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA.
38
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
39
Sarcoma Research Group, Molecular Oncology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
40
Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA.
41
INSERM, U900, Paris, France.
42
Ecole des Mines ParisTech, Fontainbleau, France.

Abstract

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.

KEYWORDS:

Ewing sarcoma; development; epigenetics; microenvironment; therapy

PMID:
26802024
PMCID:
PMC4890991
DOI:
10.18632/oncotarget.6937
[Indexed for MEDLINE]
Free PMC Article

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