Our study shows that in synovial sarcoma models, the combination of HDAC and proteasome inhibition functionally dissociates the oncogenic driving complex, reactivates tumor suppressor gene expression, and elicits ER stress, elevated ROS levels, and pro-apoptotic factor induction, resulting in significant cell death even at very low drug concentrations (Fig 6F). This evidence concerns the gene HDAC9 and synovial sarcoma.