Combined mTOR and MEK inhibition is an effective therapy in a novel mouse model for angiosarcoma.

Combined mTOR and MEK inhibition is an effective therapy in a novel mouse model for angiosarcoma. Oncotarget. 2018 May 15;9(37):24750-24765 Authors: Chadwick ML, Lane A, Thomas D, Smith AR, White AR, Davidson D, Feng Y, Boscolo E, Zheng Y, Adams DM, Gupta A, Veillette A, Chow LML Abstract Angiosarcoma is an aggressive malignancy of vascular origin that occurs de novo or in the context of previous cancer therapy. Despite multi-modal aggressive treatment including surgical resection, chemotherapy, and radiation, five-year overall survival remains poor at 35%. Due to its rarity, little is known about its molecular pathology and clinical trials have been extremely difficult to conduct. Development of animal models for rare diseases like angiosarcoma is critical to improve our understanding of tumorigenesis and to test novel treatment regimens. A genetically engineered mouse model for angiosarcoma was generated by conditional deletion of Trp53, Pten, and Ptpn12 in endothelial cells. Tumors arising from these mice recapitulate the histology and molecular pathology of the human disease including hyperactivation of the PI3K/mTOR and MAPK signaling pathways. Treatment of tumor-bearing mice with mTOR or MEK inhibitors effectively inactivated signaling and resulted in reduced proliferation and elevated apoptosis leading to tumor regression. The effect of treatment on tumor growth was transient and proliferation was restored after a period of do...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research