Molecular characterization of soft tissue sarcoma and the potential clinical applications

STS are rare,malignant tumours of mesenchymal origin which account for less than 1% of all adult malignancies. They exhibit a great clinical, histological and molecular heterogeneity, with more than 50 subtypes described. In case of advanced disease, chemotherapy has only limited effect on the overall survival of sarcoma patients with response rates below 15%. Newer compounds, especially targeted agents, may show superior efficacy, but secondary resistance occurs with time in majority of cases and up to now little is known about the mechanisms underlying this primary and secondary resistance in STS. The current research project will explore the molecular characterisation of selected STS subtypes using comprehensive analysis including miRNA profiling, whole-exome sequencing and tissue microarrays (TMA). This will allow us to understand the natural history of tumours, to study the disease evolution and to identify novel prognostic biomarkers and potential therapeutic targets for different tumour subtypes. In a second step, the proposed targets will be validated in vivo, using the established PDX models to test different therapeutic agents which are thought to be able to overcome resistance. The ultimate goal of the proposed research project is to understand and overcome therapeutic resistance in STS patients, ultimately leading to the improvement of treatment and outcome in patients with STS.