Current Management and Molecular Targets of Synovial Sarcoma

Review Article

Austin J Cancer Clin Res 2014;1(2): 1008.

Current Management and Molecular Targets of Synovial Sarcoma

Lange SES1, Kremer JC1, Schenone AD1,2, Schultze MB1 and Brian A Van Tine 1,3*

1Department of Internal Medicine and Medical Oncology. Washington University, USA

2College of Medicine, Des Moines University, USA

3Siteman Cancer Center, Washington University School of Medicine, USA

*Corresponding author: Brian A Van Tine, Department of Medicine, Division of Medical Oncology, Washington University in St. Louis School of Medicine, 660 S Euclid, Campus Box 8007, St. Louis, MO 63110, USA

Received: March 17, 2014; Accepted: April 17, 2014; Published: April 21, 2014


Synovial Sarcoma (SS) is a rare and aggressive form of soft tissue sarcoma (STS) with a high metastatic potential that is characterized by a unique translocation between SYT on chromosome 18 and SSX on chromosome X. Presently, standard of care involves surgery, radiation therapy and chemotherapy. For those patients with metastatic disease, standard of care remains enrollment in a clinical trial. While there are numerous open clinical trials for the treatment of STS in general, clinical trials designed specifically for SS remain limited. The overall low response rate to cytotoxic chemotherapies has necessitated the need for development of pathway–specific targeted therapies for SS. Deregulation of several cell signaling pathways have been identified in SS, including the SRC, Bcl–2, and MDM2 signaling pathways, which are involved with cell growth, apoptosis, and p53 regulation, respectively. Additionally, several potential enzymatic targets have been identified, including argininosuccinate synthetase 1 and histone deacetylases. Here we present an updated review of the current therapy and the prospective molecular therapeutic targets that are available for clinical trial development in SS.

Keywords: Molecular Targets; Synovial Sarcoma; Deacetylases


Synovial Sarcoma (SS) is a rare and aggressive form of soft tissue sarcoma (STS) with a high metastatic potential that frequently develops in young people between the ages of fifteen and forty [1,2]. The incidence of SS is estimated at 900–1000 cases per year in the United States and it accounts for 8–10% of the soft tissue sarcoma patient population. Though SS is not associated with an identifiable etiologic agent or genetic predisposition, it has been associated with a gene fusion product between transcription factors SYT and SSX1, SSX2, or SSX4. This translocation has been identified in 90– 95% of all SS, and is pathognomonic and diagnostic for the disease [3]. Currently, the standard therapeutic approach to local primary disease and locally recurrent disease relies upon aggressive surgical resection, with neoadjuvant or adjuvant radiation and chemotherapy. However, in a majority of metastatic SS cases, clinical trial enrollment remains the standard of care with systemic chemotherapy remaining the sole therapeutic option off–trial. Unfortunately, the prognosis for patients presenting with metastatic disease remains poor, with a median time to cancer–specific death ranging from 10–22 months [1]. These findings highlight the need for more effective, less toxic systemic therapies for SS. In 2005, a well written work by Fukukawa et al. [4] analyzed several genes up–regulated in SS and postulated upon putative molecules for the development of novel therapies to treat SS [4]. Here, almost 10 years later, we present an updated review of the prospective molecular therapeutic targets for the treatment of SS.

Synovial Sarcoma Biology

Genetics ⁄translocation biology

SS harbors a pathognomonic chromosomal translocation t(x;18) (p11.2;q11.2) that results in a fusion between the SYT gene on chromosome 18 and one of three homologous genes (SSX1, SSX2, SSX4) on the X chromosome (Figure 1). The SYT–SSX translocation has been identified in approximately 95% of SS, and is the only cytogenetic abnormality in one–third of cases [3]. Most cases of SYT–SSX translocation associated SS harbor a fusion between SYT and SSX1 or SSX2, up to 10% of cases carry both translocations, and only rare cases carry the SYT–SSX4 translocation [5]. The anatomy of this SYT–SSX fusion oncogene has been extensively studied to better understand its pathogenicity, and it has been linked to aberrant E–cadherin repression, over expression of Bcl–2, and down–regulationof Mcl1 [6,7].