Soft tissue sarcomas are rare neoplasms consisting of more than 50 histological subtypes and can arise in any part of the body. Despite optimal treatment of non-metastatic, high-grade soft tissue sarcomas, about 50- 80% of patients relapse, either locally or in distant organs (metastases). Irrespective of the multiple sarcoma subtypes at different anatomical locations, their most frequent site of metastasis are the lungs [1], About 70% of sarcoma patients develop lung metastases and overt lung metastases are also often the cause of death indicating that the development of lung metastases is an important determinant of prognosis and survival in sarcoma patients. Once metastasized, systemic therapy (chemotherapy, targeted therapy) is the only remaining treatment option. However, response rates are quite low (15-20% max) and the median overall survival is 15 months [2], Despite trials with new compounds or combinations, survival rates have stagnated over the past 20 years. One of the main reasons is the lack of biomarkers that predicts the efficacy of standard treatment options, often leading to a trial and error' approach in which treatment side effects are the only certainty.

Extracellular vesicles (EVs) are nanovesicles secreted in high numbers by cancer cells. They are involved in the development and progression of cancer and its response to therapeutic intervention. EVs enter the bloodstream and show promising predictive or prognostic value for patient follow-up [3], Although EVs have been studied in many cancers, literature regarding the role of EVs in sarcoma is scarce and mainly limited to Ewing sarcoma and osteosarcoma [4,5],

With our study, we wish to explore the role of sarcoma-derived EVs during different stages of the clinical course of sarcoma patients. In particular, our research will be focused on the role of EVs in pre-metastatic niche formation and development of lung metastases. In addition, we wish to develop a faithful and representative preclinical sarcoma model to test standard and experimental compounds. For this, we will perform a co-clinical trial with accepted (but time-consuming) models in literature such as patient-derived (orthotopic) xenografts (PD(o)X) to validate our in-house designed chick chorio-allantois membrane model (CAM-assay) to deliver relevant therapeutic answers in a time window of 14 days and provide a quick acces to effective treatments