Activity Of Mk1775, A Selective Wee1 Inhibitor, Alone Or In Combination With Gemcitabine, In Sarcomas.

10084 Background: Sarcomas consist of more than 50 subtypes of mesenchymal tumors. Doxorubicin alone or in combination has been the primary therapy for treatment of sarcomas; however, the response rates are suboptimal in many of the more common adult subtypes of soft tissue sarcoma. Accordingly, new agents are needed for the treatment of this heterogeneous group of diseases. Wee1 is a critical component of the G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of CDC2. Methods: MK1775 treatment of multiple sarcoma preclinical models at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death. In our current study we have investigated the therapeutic efficacy of MK1775 in sarcoma cell lines, patient-derived tumor explants ex vivo and in vivo in a xenograft model of osteosarcoma both alone and in combination with gemcitabine. Results: In patient-derived bone and soft tissue sarcoma samples ex vivo treat...