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

Heinrich Kovar 1, 2, * James Amatruda 3 Erika Brunet 4 Stefan Burdach 5 Florencia Cidre-Aranaz 6 Enrique de Alava 7 Uta Dirksen 8 Wietske van der Ent 9, 10 Patrick Grohar 11 Thomas Grünewald 12 Lee Helman 13 Peter Houghton 14 Kristiina Iljin 15 Eberhard Korsching 16 Marc Ladanyi 17 Elizabeth Lawlor 18 Stephen Lessnick 19 Joseph Ludwig 20 Paul Meltzer 21 Markus Metzler 22 Jaume Mora 23 Richard Moriggl 24, 25 Takuro Nakamura 26 Theodore Papamarkou 27 Branka Sarikas 28 Françoise Rédini 29 Guenther Richter 5 Claudia Rossig 8 Keri Schadler 30 Beat Schäfer 31 Katia Scotlandi 32 Nathan Sheffield 28 Anang Shelat 33 Ewa Snaar-Jagalska 10 Poul Sorensen 34 Kimberly Stegmaier 35 Elizabeth Stewart 36 Alejandro Sweet-Cordero 37 Karoly Szuhai 38 Oscar Tirado 39 Franck Tirode 9 Jeffrey Toretsky 40 Kalliopi Tsafou 40 Aykut Üren 40 Andrei Zinovyev 9, 41 Olivier Delattre 9
* Corresponding author
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Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies.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.
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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, Impact journals, 2016, 7 (8), pp.8613-24. ⟨10.18632/oncotarget.6937⟩. ⟨inserm-01703282⟩

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