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

Heinrich Kovar, James Amatruda, Erika Brunet, Stefan Burdach, Florencia Cidre-Aranaz, Enrique De Alava, Uta Dirksen, Wietske Van Der Ent, Patrick Grohar, Thomas G.P. Grünewald, Lee Helman, Peter Houghton, Kristiina Iljin, Eberhard Korsching, Marc Ladanyi, Elizabeth Lawlor, Stephen Lessnick, Joseph Ludwig, Paul Meltzer, Markus MetzlerJaume Mora, Richard Moriggl, Takuro Nakamura, Theodore Papamarkou, Branka Radic Sarikas, Francoise Rédini, Guenther H.S. Richter, Claudia Rossig, Keri Schadler, Beat W. Schäfer, Katia Scotlandi, Nathan C. Sheffield, Anang Shelat, Ewa Snaar-Jagalska, Poul Sorensen, Kimberly Stegmaier, Elizabeth Stewart, Alejandro Sweet-Cordero, Karoly Szuhai, Oscar M. Tirado, Franck Tirode, Jeffrey Toretsky, Kalliopi Tsafou, Aykut Üren, Andrei Zinovyev, Olivier Delattre

Research output: Contribution to journalArticle

23 Scopus citations

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Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies.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. RNAsequencing 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.

Original languageEnglish (US)
Pages (from-to)8613-8624
Number of pages12
JournalOncotarget
Volume7
Issue number8
DOIs
StatePublished - Jan 1 2016

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Keywords

  • Development
  • Epigenetics
  • Ewing sarcoma
  • Microenvironment
  • Therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Kovar, H., Amatruda, J., Brunet, E., Burdach, S., Cidre-Aranaz, F., De Alava, E., Dirksen, U., Van Der Ent, W., Grohar, P., Grünewald, T. G. P., Helman, L., Houghton, P., Iljin, K., Korsching, E., Ladanyi, M., Lawlor, E., Lessnick, S., Ludwig, J., Meltzer, P., ... Delattre, O. (2016). The second European interdisciplinary Ewing sarcoma research summit - A joint effort to deconstructing the multiple layers of a complex disease. Oncotarget, 7(8), 8613-8624. https://doi.org/10.18632/oncotarget.6937