Given the previously reported effects of SS18-SSX on epigenetic gene silencing [12–15] and the significance of the AKT signaling pathway in SS [23], we sought to determine the effects of vorinostat (HDAC inhibitor) and ridaforolimus (mTOR inhibitor) as single agents, in combination with each other, and in combination with cytotoxic chemotherapies commonly used to treat SS. Here, MTOR is linked to synovial sarcoma.