The First European Interdisciplinary Ewing Sarcoma Research Summit

The European Network for Cancer Research in Children and Adolescents (ENCCA) provides an interaction platform for stakeholders in research and care of children with cancer. Among ENCCA objectives is the establishment of biology-based prioritization mechanisms for the selection of innovative targets, drugs, and prognostic markers for validation in clinical trials. Specifically for sarcomas, there is a burning need for novel treatment options, since current chemotherapeutic treatment protocols have met their limits. This is most obvious for metastatic Ewing sarcoma (ES), where long term survival rates are still below 20%. Despite significant progress in our understanding of ES biology, clinical translation of promising laboratory results has not yet taken place due to fragmentation of research and lack of an institutionalized discussion forum. To fill this gap, ENCCA assembled 30 European expert scientists and five North American opinion leaders in December 2011 to exchange thoughts and discuss the state of the art in ES research and latest results from the bench, and to propose biological studies and novel promising therapeutics for the upcoming European EWING2008 and EWING2012 clinical trials.

[1]  B. Schäfer,et al.  Small‐molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma , 2012, International journal of cancer.

[2]  M. Aichler,et al.  High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients. , 2012 .

[3]  M. Aichler,et al.  High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[4]  M. Ferracin,et al.  miR‐34a predicts survival of Ewing's sarcoma patients and directly influences cell chemo‐sensitivity and malignancy , 2012, The Journal of pathology.

[5]  E. Álava,et al.  1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma , 2012, Oncogene.

[6]  U. Dirksen,et al.  The ganglioside antigen GD2 is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting , 2012, British Journal of Cancer.

[7]  F. Clavel-Chapelon,et al.  Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma , 2012, Nature Genetics.

[8]  C. Pellat-deceunynck,et al.  A Functional, New Short Isoform of Death Receptor 4 in Ewing's Sarcoma Cell Lines May be Involved in TRAIL Sensitivity/Resistance Mechanisms , 2012, Molecular Cancer Research.

[9]  Yuping Zhang,et al.  Cytoplasmic Metadherin (MTDH) Provides Survival Advantage under Conditions of Stress by Acting as RNA-binding Protein* , 2011, The Journal of Biological Chemistry.

[10]  Martin Pule,et al.  Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. , 2011, Blood.

[11]  B. Martín-Castillo,et al.  Metformin: Multi-faceted protection against cancer , 2011, Oncotarget.

[12]  J. Highley,et al.  Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathology , 2011, Acta Neuropathologica.

[13]  A. Sickmann,et al.  STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors , 2011, Molecular Cancer Research.

[14]  S. Rosenberg,et al.  Treating cancer with genetically engineered T cells. , 2011, Trends in biotechnology.

[15]  A. Llombart‐Bosch,et al.  Notch signalling is off and is uncoupled from HES1 expression in Ewing's sarcoma , 2011, The Journal of pathology.

[16]  G. Schwartz,et al.  Targeting of insulin-like growth factor type 1 receptor in Ewing sarcoma: unfulfilled promise or a promising beginning? , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  A. Üren,et al.  Novel peptide binds EWS-FLI1 and reduces the oncogenic potential in Ewing tumors , 2011, Cell cycle.

[18]  P. Sorensen,et al.  The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis , 2011, Cell Death and Differentiation.

[19]  Hans Clevers,et al.  Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling , 2011, Nature.

[20]  A. Burgess,et al.  LGR5 Is a Negative Regulator of Tumourigenicity, Antagonizes Wnt Signalling and Regulates Cell Adhesion in Colorectal Cancer Cell Lines , 2011, PloS one.

[21]  Qing-Rong Chen,et al.  Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening. , 2011, Journal of the National Cancer Institute.

[22]  P. Lollini,et al.  Efficacy of and resistance to anti-IGF-1R therapies in Ewing's sarcoma is dependent on insulin receptor signaling , 2011, Oncogene.

[23]  Hans Clevers,et al.  The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. , 2011, Cell stem cell.

[24]  D. Strunk,et al.  Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma , 2011, Oncogene.

[25]  D. Busch,et al.  Specific recognition and inhibition of Ewing tumour growth by antigen-specific allo-restricted cytotoxic T cells , 2011, British Journal of Cancer.

[26]  P. Sorensen,et al.  Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas. , 2010, Cancer research.

[27]  O. Delattre,et al.  Zoledronic acid as a new adjuvant therapeutic strategy for Ewing's sarcoma patients. , 2010, Cancer research.

[28]  K. Hunter,et al.  Modeling metastasis biology and therapy in real time in the mouse lung. , 2010, The Journal of clinical investigation.

[29]  U. Dirksen,et al.  Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Axel Imhof,et al.  Phosphorylation of histone H3T6 by PKCβI controls demethylation at histone H3K4 , 2010, Nature.

[31]  T. Triche,et al.  CD133 expression in chemo-resistant Ewing sarcoma cells , 2010, BMC Cancer.

[32]  D. Campana,et al.  2B4 (CD244) Signaling by Recombinant Antigen-specific Chimeric Receptors Costimulates Natural Killer Cell Activation to Leukemia and Neuroblastoma Cells , 2009, Clinical Cancer Research.

[33]  A. Üren,et al.  Small molecule selected to disrupt oncogenic protein EWS-FLI1 interaction with RNA Helicase A inhibits Ewing's Sarcoma , 2009, Nature Medicine.

[34]  T. Triche,et al.  Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition. , 2009, Cancer cell.

[35]  Nicolò Riggi,et al.  Identification of cancer stem cells in Ewing's sarcoma. , 2009, Cancer research.

[36]  K. Stegmaier,et al.  Phase II study of intermediate‐dose cytarabine in patients with relapsed or refractory Ewing sarcoma: A report from the Children's Oncology Group , 2009, Pediatric blood & cancer.

[37]  Samuel Kaski,et al.  Combined use of expression and CGH arrays pinpoints novel candidate genes in Ewing sarcoma family of tumors , 2009, BMC Cancer.

[38]  P. Lin,et al.  EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model. , 2008, Cancer research.

[39]  M. Kauer,et al.  EWS-FLI1 suppresses NOTCH-activated p53 in Ewing's sarcoma. , 2008, Cancer research.

[40]  S. Burchill,et al.  Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's sarcoma family of tumors: A study by the United Kingdom Cancer Cytogenetics and the Children's Cancer and Leukaemia Group , 2008, Genes, chromosomes & cancer.

[41]  Lauren Long,et al.  Interferon- (cid:1) Sensitizes Resistant Ewing’s Sarcoma Cells to Tumor Necrosis Factor Apoptosis-Inducing Ligand-Induced Apoptosis by Up-Regulation of Caspase-8 Without Altering Chemosensitivity , 2007 .

[42]  Todd R Golub,et al.  Signature-Based Small Molecule Screening Identifies Cytosine Arabinoside as an EWS/FLI Modulator in Ewing Sarcoma , 2007, PLoS medicine.

[43]  C. Thiele,et al.  Interferon γ Enhances the Effectiveness of Tumor Necrosis Factor-Related Apoptosis–Inducing Ligand Receptor Agonists in a Xenograft Model of Ewing’s Sarcoma , 2004, Cancer Research.

[44]  C. Thiele,et al.  Induction of caspase 8 by interferon gamma renders some neuroblastoma (NB) cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membrane TR1/TR2 also contributes to TRAIL resistance in NB. , 2003, Cancer research.

[45]  S. Knuutila,et al.  Prognostic impact of chromosomal aberrations in Ewing tumours , 2002, British Journal of Cancer.

[46]  G. Thomas,et al.  Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours , 1992, Nature.

[47]  S. Economou,et al.  Mithramycin in the treatment of metastatic ewing's sarcoma , 1973, Cancer.

[48]  M. Kalos.  Muscle CARs and TcRs: turbo-charged technologies for the (T cell) masses , 2011, Cancer Immunology, Immunotherapy.

[49]  A. Üren,et al.  A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing’s sarcoma , 2009 .

[50]  P. Lin,et al.  EWS-FLI 1 Induces Developmental Abnormalities and Accelerates Sarcoma Formation in a Transgenic Mouse Model , 2008 .

[51]  K. Bhatia,et al.  Enhanced poly(adenosine diphosphate ribose) polymerase activity and gene expression in Ewing's sarcoma cells. , 1990, Cancer research.