Bone and soft tissue sarcomas (B-STS) are a rare and heterogeneous group of tumors. As of today, a multidisciplinary treatment encompassing complete surgical removal of the tumor +/- chemotherapy and radiotherapy cures roughly 50% of patients. Unfortunately, the most active chemotherapies may eradicate micro-metastatic disease, but do not cure non-resectable disease. Several second- and further-line treatments have been tested showing marginal activity at most. Therefore, innovative therapeutic strategies are urgently needed.