Of mice and men: Opportunities to use genetically engineered mouse models of synovial sarcoma for preclinical cancer therapeutic evaluation

Abstract

Background: Synovial sarcoma is a soft tissue malignancy with a predilection for adolescents and young adults. Despite recent improvements in the understanding of its character and etiology, few therapeutic advances have been made. The mortality rate is high among the young population it affects. The low incidence of most subtypes of sarcoma, such as synovial sarcoma, makes disease-specifi c trials diffi cult to organize. The biological differences between sarcoma subtypes make inclusion of multiple types in general trials unsatisfactory as well. Methods: A review of the literature regarding targetable pathways in synovial sarcoma was undertaken. A strategy has been devised to utilize available technologies in order to prioritize drug trial planning. Results: Cell culture and xenograft research with synovial sarcoma cell lines have identifi ed some critical pathways that may be targetable. Promising therapeutic strategies include newer cytotoxic chemotherapies, antiangiogenic agents, anti-IGF1R pathway agents, anti-Bcl-2/proapoptotic agents, and histone deacetylase complex inhibitors. Conclusions: We propose to prioritize potential therapeutic strategies via preclinical testing of agents in a genetic mouse model of synovial sarcoma. Preclinical optimization of treatment regimens can guide the development of more focused patient trials.