+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival.

          Related collections

          Most cited references429

          • Record: found
          • Abstract: found
          • Article: not found

          Signatures of mutational processes in human cancer

          All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.
            • Record: found
            • Abstract: found
            • Article: not found

            Tumour exosome integrins determine organotropic metastasis

            Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
              • Record: found
              • Abstract: found
              • Article: not found

              Cancer immunotherapy: harnessing the immune system to battle cancer.

              The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.

                Author and article information

                Role: Academic Editor
                J Clin Med
                J Clin Med
                Journal of Clinical Medicine
                14 April 2021
                April 2021
                : 10
                : 8
                : 1685
                [1 ]Pediatrics III, University Hospital Essen, 45147 Essen, Germany; Uta.Dirksen@ 123456uk-essen.de
                [2 ]West German Cancer Center (WTZ), University Hospital Essen, 45147 Essen, Germany; sebastian.bauer@ 123456uk-essen.de (S.B.); stephane.collaud@ 123456rlk.uk-essen.de (S.C.); jendrik.hardes@ 123456uk-essen.de (J.H.); Arne.Streitbuerger@ 123456uk-essen.de (A.S.); beate.timmermann@ 123456uk-essen.de (B.T.)
                [3 ]German Cancer Consortium (DKTK), Essen/Düsseldorf, University Hospital Essen, 45147 Essen, Germany
                [4 ]Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA; jamatruda@ 123456chla.usc.edu
                [5 ]Department of Medical Oncology, Sarcoma Center, University Hospital Essen, 45147 Essen, Germany
                [6 ]Department of Thoracic Surgery, Ruhrlandklinik, University of Essen-Duisburg, 45239 Essen, Germany
                [7 ]Institute of Biomedicine of Sevilla (IbiS), Virgen del Rocio University Hospital, CSIC, University of Sevilla, CIBERONC, 41013 Seville, Spain; enrique.alava.sspa@ 123456juntadeandalucia.es
                [8 ]Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 41009 Seville, Spain
                [9 ]Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA 02215, USA; Steven_DuBois@ 123456dfci.harvard.edu (S.G.D.); David_Shulman@ 123456dfci.harvard.edu (D.S.S.)
                [10 ]Department of Musculoskeletal Oncology, Sarcoma Center, 45147 Essen, Germany
                [11 ]Division of Translational Pathology, Gerhard-Domagk Institute of Pathology, University Hospital Münster, 48149 Münster, Germany; wolfgang.hartmann@ 123456ukmuenster.de
                [12 ]West German Cancer Center (WTZ), Network Partner Site, University Hospital Münster, 48149 Münster, Germany
                [13 ]St. Anna Children’s Cancer Research Institute and Medical University Vienna, 1090 Vienna, Austria; heinrich.kovar@ 123456ccri.at
                [14 ]Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany; Markus.Metzler@ 123456uk-erlangen.de
                [15 ]Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre, 45147 Essen, Germany
                [16 ]Departments of Oncology and Pediatrics, Georgetown University, Washington, DC 20057, USA; jat42@ 123456georgetown.edu
                [17 ]St. Josefs Hospital Bochum, University Hospital, 44791 Bochum, Germany; yasmin.uhlenbruch@ 123456klinikum-bochum.de
                [18 ]Department of Radiology, Klinikum Ibbenbüren, 49477 Ibbenbühren, Germany; v.vieth@ 123456klinikum-ibbenbueren.de
                [19 ]Division of Translational Pediatric Sarcoma Research, Hopp-Children’s Cancer Center Heidelberg (KiTZ), 69120 Heidelberg, Germany; t.gruenewald@ 123456kitz-heidelberg.de
                [20 ]Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
                [21 ]Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
                [22 ]German Cancer Consortium (DKTK), Core Center, 69120 Heidelberg, Germany
                Author notes

                Equal contribution.

                Author information
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                : 03 March 2021
                : 31 March 2021

                ewing sarcoma,small round cell sarcoma,limb salvage,metastasis,ewsr1-fli1,chromosomal translocation,fusion protein,transcription,splicing


                Comment on this article