Related Experiment Video
Updated: Feb 23, 2026
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
[Functional genomics of Ewing sarcoma]
1Max-Eder Nachwuchsgruppe für Pädiatrische Sarkombiologie, Pathologisches Institut, Medizinische Fakultät, LMU München, Thalkirchner Str. 36, 80337, München, Deutschland. thomas.gruenewald@med.uni-muenchen.de.
Abstract:
Ewing sarcoma is a highly aggressive bone or soft-tissue tumor mostly occurring in children and adolescents. Conventional multi-modal therapies are associated with considerable acute and chronic toxicity. Thus, more effective and in particular less toxic therapeutic strategies are urgently required. Despite the fact that Ewing sarcoma is characterized by specific EWSR1-ETS gene fusions, the resulting fusion oncoproteins are not suitable for targeted therapy due to their low immunogenicity and the ubiquitous expression of their constituents. However, functional genomics revealed several EWSR1-ETS target genes, which are only minimally expressed in normal tissues, and which could serve as surrogate-targets for (immuno-)therapeutic approaches. Moreover, functional genomic analyses yielded first mechanistic explanations for the relatively high incidence of Ewing sarcoma in Europeans, and first studies are exploring the value of circulating free DNA and/or exosomal mRNA of EWSR1-ETS fusion oncogenes as minimal-residual-disease markers in Ewing sarcoma. This review summarizes key contributions to these aspects and gives a perspective on their medical relevance.
Insights
New therapeutic strategies are needed for Ewing sarcoma, a rare childhood cancer. Researchers are exploring EWSR1-ETS target genes as potential therapeutic targets and biomarkers for minimal residual disease.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Ewing sarcoma is an aggressive pediatric cancer with significant treatment toxicities.
- Current therapies face challenges due to the nature of EWSR1-ETS fusion oncoproteins.
- There is a critical need for more effective and less toxic treatment options.
Purpose of the Study:
- To review therapeutic strategies targeting EWSR1-ETS fusion genes in Ewing sarcoma.
- To explore novel surrogate targets and biomarkers for Ewing sarcoma.
- To discuss the medical relevance of recent findings in Ewing sarcoma research.
Main Methods:
- Review of functional genomics studies.
- Analysis of EWSR1-ETS target gene expression.
- Investigation of circulating free DNA and exosomal mRNA markers.
Main Results:
- Identification of EWSR1-ETS target genes as potential therapeutic surrogates.
- Mechanistic insights into Ewing sarcoma incidence in Europeans.
- Emerging role of cell-free DNA and exosomal mRNA in minimal residual disease detection.
Conclusions:
- EWSR1-ETS target genes offer promising avenues for novel (immuno-)therapies.
- Biomarkers for minimal residual disease are under active investigation.
- Further research holds potential for improved Ewing sarcoma management.
