Sarcomas are mainly divided into two types, bone sarcoma and soft-tissue sarcoma. Sarcomas display remarkable genetic and histologic diversity, as reflected by more than 150 subtypes according to the World Health Organization Classification, which in turn poses significant diagnostic and therapeutic difficulties. “Actionable” lesions that allow prediction of response to conventional or targeted anti-cancer drugs and/or represent direct targets for therapeutic intervention are lacking in the majority of cases due to incomplete understanding of the events that drive sarcoma development.
The Precision Sarcoma Research group funded by the Emmy Noether Program of the German Research Foundation (DFG) has been established with the aim to better understand the molecular alterations underlying tumor development and to identify novel targets for precision cancer therapy. To this end, we employ tumor multi-omics data generated within the in-house precision oncology workflows, in particular the NCT/German Cancer Consortium (DKTK) MASTER (Molecularly Aided Stratification for Tumor Eradication) as well as publicly available data resources to systematically investigate the genomic, epigenomic, transcriptomic and immunologic landscapes of sarcomas to identify pan-sarcoma or sub-entity specific pathognomonic alterations. In a project-specific manner, we have applied latest technology platforms at the DKFZ, such as long-read sequencing, single nuclei sequencing as well as spatial proteomics, to gain deeper insights into the biology of the tumors. Mechanistic investigations of selected aberrations is enabled by our expanding model system panel and comprehensive toolkit enabling functional genomics investigations (e.g. CRISPR/Cas9 libraries).
We are currently pursuing the following objectives:
- Targeting critical disease processes: Focus – Activated telomere maintenance mechanisms
- Integrative multi-omics characterization: Focus – Ultra-rare sarcoma
- Development of innovative therapeutic approaches: Focus – Targeted protein degradation, individualized immuno-therapeutics
These studies will improve the understanding of sarcomagenesis and identify targets for biological stratification and molecular mechanism-guided therapeutic intervention.
