The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease
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Ewing sarcoma research summit” assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identificatio...
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| Format: | Online |
| Language: | English |
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Impact Journals LLC
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890991/ |
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pubmed-4890991 |
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pubmed-48909912016-06-20 The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease Kovar, Heinrich Amatruda, James Brunet, Erika Burdach, Stefan Cidre-Aranaz, Florencia de Alava, Enrique Dirksen, Uta van der Ent, Wietske Grohar, Patrick Grünewald, Thomas G. P. Helman, Lee Houghton, Peter Iljin, Kristiina Korsching, Eberhard Ladanyi, Marc Lawlor, Elizabeth Lessnick, Stephen Ludwig, Joseph Meltzer, Paul Metzler, Markus Mora, Jaume Moriggl, Richard Nakamura, Takuro Papamarkou, Theodore Sarikas, Branka Radic Rédini, Francoise Richter, Guenther H. S. Rossig, Claudia Schadler, Keri Schäfer, Beat W. Scotlandi, Katia Sheffield, Nathan C. Shelat, Anang Snaar-Jagalska, Ewa Sorensen, Poul Stegmaier, Kimberly Stewart, Elizabeth Sweet-Cordero, Alejandro Szuhai, Karoly Tirado, Oscar M. Tirode, Franck Toretsky, Jeffrey Tsafou, Kalliopi Üren, Aykut Zinovyev, Andrei Delattre, Olivier Review 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Ewing sarcoma research summit” assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies.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. Impact Journals LLC 2016-01-18 /pmc/articles/PMC4890991/ /pubmed/26802024 http://dx.doi.org/10.18632/oncotarget.6937 Text en Copyright: © 2016 Kovar et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kovar, Heinrich Amatruda, James Brunet, Erika Burdach, Stefan Cidre-Aranaz, Florencia de Alava, Enrique Dirksen, Uta van der Ent, Wietske Grohar, Patrick Grünewald, Thomas G. P. Helman, Lee Houghton, Peter Iljin, Kristiina Korsching, Eberhard Ladanyi, Marc Lawlor, Elizabeth Lessnick, Stephen Ludwig, Joseph Meltzer, Paul Metzler, Markus Mora, Jaume Moriggl, Richard Nakamura, Takuro Papamarkou, Theodore Sarikas, Branka Radic Rédini, Francoise Richter, Guenther H. S. Rossig, Claudia Schadler, Keri Schäfer, Beat W. Scotlandi, Katia Sheffield, Nathan C. Shelat, Anang Snaar-Jagalska, Ewa Sorensen, Poul Stegmaier, Kimberly Stewart, Elizabeth Sweet-Cordero, Alejandro Szuhai, Karoly Tirado, Oscar M. Tirode, Franck Toretsky, Jeffrey Tsafou, Kalliopi Üren, Aykut Zinovyev, Andrei Delattre, Olivier |
| spellingShingle |
Kovar, Heinrich Amatruda, James Brunet, Erika Burdach, Stefan Cidre-Aranaz, Florencia de Alava, Enrique Dirksen, Uta van der Ent, Wietske Grohar, Patrick Grünewald, Thomas G. P. Helman, Lee Houghton, Peter Iljin, Kristiina Korsching, Eberhard Ladanyi, Marc Lawlor, Elizabeth Lessnick, Stephen Ludwig, Joseph Meltzer, Paul Metzler, Markus Mora, Jaume Moriggl, Richard Nakamura, Takuro Papamarkou, Theodore Sarikas, Branka Radic Rédini, Francoise Richter, Guenther H. S. Rossig, Claudia Schadler, Keri Schäfer, Beat W. Scotlandi, Katia Sheffield, Nathan C. Shelat, Anang Snaar-Jagalska, Ewa Sorensen, Poul Stegmaier, Kimberly Stewart, Elizabeth Sweet-Cordero, Alejandro Szuhai, Karoly Tirado, Oscar M. Tirode, Franck Toretsky, Jeffrey Tsafou, Kalliopi Üren, Aykut Zinovyev, Andrei Delattre, Olivier The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease |
| author_facet |
Kovar, Heinrich Amatruda, James Brunet, Erika Burdach, Stefan Cidre-Aranaz, Florencia de Alava, Enrique Dirksen, Uta van der Ent, Wietske Grohar, Patrick Grünewald, Thomas G. P. Helman, Lee Houghton, Peter Iljin, Kristiina Korsching, Eberhard Ladanyi, Marc Lawlor, Elizabeth Lessnick, Stephen Ludwig, Joseph Meltzer, Paul Metzler, Markus Mora, Jaume Moriggl, Richard Nakamura, Takuro Papamarkou, Theodore Sarikas, Branka Radic Rédini, Francoise Richter, Guenther H. S. Rossig, Claudia Schadler, Keri Schäfer, Beat W. Scotlandi, Katia Sheffield, Nathan C. Shelat, Anang Snaar-Jagalska, Ewa Sorensen, Poul Stegmaier, Kimberly Stewart, Elizabeth Sweet-Cordero, Alejandro Szuhai, Karoly Tirado, Oscar M. Tirode, Franck Toretsky, Jeffrey Tsafou, Kalliopi Üren, Aykut Zinovyev, Andrei Delattre, Olivier |
| author_sort |
Kovar, Heinrich |
| title |
The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease |
| title_short |
The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease |
| title_full |
The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease |
| title_fullStr |
The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease |
| title_full_unstemmed |
The second European interdisciplinary Ewing sarcoma research summit – A joint effort to deconstructing the multiple layers of a complex disease |
| title_sort |
second european interdisciplinary ewing sarcoma research summit – a joint effort to deconstructing the multiple layers of a complex disease |
| description |
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. |
| publisher |
Impact Journals LLC |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890991/ |
| _version_ |
1613588017418600448 |