Recent Advances in Synovial Sarcoma: Molecular Insights and Evolving Pharmacological Therapies

Synovial sarcoma (SS) is a soft-tissue carcinoma primarily affecting teenagers and young adults caused by three oncoprotein fusions: SS18-SSX1, SS18-SSX2, or SS18-SSX4. The tumors may be monophasic, biphasic, or poorly differentiated. There are numerous treatments available, including targeted medications, immunotherapies, and metabolic therapy. However, further study is required to better understand tumor biology, uncover predictive biomarkers, and enhance patient outcomes. Recent developments in SS research have significantly advanced our understanding and management of this challenging malignancy. Advances in genomic sequencing have elucidated the complex molecular landscape of SS, revealing additional genetic mutations and epigenetic alterations that contribute to tumor progression. Notably, research has focused on the role of the SS18-SSX fusion oncoproteins in altering global DNA methylation patterns and influencing chromatin remodeling via the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, opening avenues for targeted epigenetic therapies. Immunotherapy has emerged as a viable option, with research looking into the effectiveness of immune checkpoint inhibitors (ICIs), CAR-T cell therapy, and tumor-infiltrating lymphocyte (TIL) treatments. These treatments seek to improve the immune system's ability to identify and kill SS cells. In addition, innovative targeted medicines are being studied in therapeutic trials, including those that block important signaling pathways and metabolic processes specific to SS. Personalized medicine is increasingly influencing treatment tactics, with an emphasis on adapting medicines to the molecular and genetic profiles of individual cancers. This transition is supplemented by an increasing emphasis on patient-reported outcomes, with the goal of improving both survival rates and quality of life. As research progresses, these emerging trends hold promise for more effective and personalized treatment options, potentially leading to better outcomes for SS patients. In this review, we primarily address the pharmacologic treatment of SS in two settings: the curative setting, where wide surgical excision along with radiotherapy and (neo) adjuvant chemotherapy as appropriate, is the standard treatment, and the palliative setting, where the same regimen is used.