Biological, functional and clinical characterization of epithelioid sarcomas for the development of innovative and gentle therapeutic options.

An international and interdisciplinary team of young physicians, veterinarians, biologists and bioinformaticians is researching malignant soft tissue and bone tumors in young people at the German Cancer Research Center (DKFZ) Heidelberg. This includes epithelioid sarcoma (ES). The main objective is to develop gentle treatment options that, unlike conventional polychemotherapy or surgical treatments, are not associated with significant acute and chronic side effects. The implementation concept also includes close collaboration with other leading institutions in Germany and abroad. 

Since 2020, the research project has been addressing the following objectives

1. Genetic, epigenomic, and transcriptional characterization of EpS
2. Functional characterization of the identified molecular alterations and correlation with clinical data
3. Elucidation of disease-relevant mechanisms and testing of innovative therapies in preclinical models
4. Translation of the findings into individual trials and clinical studies in patients with EpS.



Project Status 2026

• To date, 126 EpS tumors (original target: 50) have been analyzed thanks to international collaborations. The delivery of additional samples is in preparation. A technique developed at the DKFZ makes it possible to analyze the complete proteome even from conventional histological tissue samples. It is expected that this globally unique dataset, including the proteome, will yield new insights into which molecular alterations, in addition to SMARCB1 defects, contribute to the development and progression of EpS.
• Configuration of a continuously expanding cell line atlas for the investigation of relevant driver mutations and cellular signaling pathways. All cell lines are to be genetically modified to conditionally re-express SMARCB1. All new cell lines will be molecularly characterized using multi-omics analyses. The goal is to enable increasingly accurate predictions of the relevance of individual alterations for further preclinical and clinical research.
• Based on a thorough analysis of the data available to date, the oncogenic transcription factor MYC appears to play a crucial role in EpS. Initial experiments with MYC-specific pharmacological inhibitors suggest that EpS cell lines respond well to treatment.
• Building on the findings to date, the goal is to identify and further characterize the central oncogenic transcription factor MYC in order to discover new therapeutic agents tailored to EpS tumor biology. Based on insights from functional genomics, these agents may enable targeted therapeutic approaches for patients with EpS.

SMARCB1 e.V. has provided nearly 150,000 euros in financial support for this innovative research project to date and has organized three international, digital expert meetings (2021, 2023, 2026) on EpS. These have contributed to the establishment of a global research consortium.

In 2026 and 2027, SMARCB1 e.V. plans to fund the research with an additional 35,000 euros each year. The nonprofit association is also counting on continued support from stakeholders across the entire social spectrum.