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Soft tissue sarcomas are rare malignancies of mesenchymal origin, which consist of approximately 50 histological subtypes.For a number of years two chemotherapeutic agents have been used to treat locally advanced and metastatic disease, namely doxorubicin and ifosfamide.The introduction of imatinib as an effective therapy for metastatic gastro intestinal stromal tumours (GIST) heralded the development of the concept of targeted therapy in solid tumours.Other rational therapies have shown efficacy in this histological sub type including sunitinib and nilotinib.Initial results of a randomized Phase Ⅲ trial have demonstrated significantly longer recurrence free survival in patients treated with adjuvant imatinib compared to placebo.Data regarding overall survival are not yet available.Further promising molecular targeted agents in sarcoma include the use of IGF 1-R (insulin-like growth factor-1 receptor) inhibitors in relapsed/refractory Ewings sarcoma.Phase Ⅰ trial results have shown promising activity of antibodies to IGF-1 R and Phase Ⅱ trials are ongoing.An anti angiogenlc agent, pazopanib, acting on the vascular endothelial growth factor receptor (VEGFR) has displayed activity in an European trial of soft tissue sarcoma patients (however, activity was not observed in those with liposarcoma).Recently presented results have shown benefit for the anti angiogenic drug (cidiranib) in alveolar soft part sarcoma, a subtype unresponsive to conventional chemotherapy.Retrospective data have suggested that trabectedin, a marine derived alkaloid that binds covalently to the DNA minor groove, has particular activity in myxoid liposarcoma.Further work is required in other translocation driven sarcomas and the selection of rationally designed drugs for specific targets in individual subtypes.