Advances of SS18-SSX fusion gene in synovial sarcoma: Emerging novel functions and therapeutic potentials

Abstract

Synovial sarcoma is a rare type of soft tissue sarcoma that primarily affects adolescents and young adults, featured by aggressive behavior and a high potential for metastasis. Genetically, synovial sarcoma is defined by the fusion oncogene SS18-SSX arising from the translocation of t(X;18)(p11;q11). SS18-SSX fusion gene is the major driver of the oncogenic event in synovial sarcoma. SS18-SSX fusion protein, while not containing any DNA-binding motifs, binds to the SWI/SNF (BAF) complex, a major epigenetic regulator, leading to the disruption of gene expression which results in tumor initiation and progression. Emerging studies on the molecular mechanisms of SS18-SSX associated signaling pathway hold promise for developments in diagnosis and treatments. Advanced diagnostic methods facilitate early and precise detection of the tumor, enabling disease monitoring and prognostic improvements. Treatment of synovial sarcoma typically comprises local surgery, radiotherapy and chemotherapy, while novel managements such as immunotherapy, targeted therapies and epigenetic modifiers are explored. This review focuses on the recent studies of SS18-SSX fusion gene, epigenetic landscape, signaling pathways, diagnostic techniques, and relevant therapeutic advances, aiming to inhibit the oncogenic processes and improve outcomes for patients with synovial sarcoma.