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Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 3/2015

01-09-2015 | Clinical

Synovial sarcoma is a gateway to the role of chromatin remodeling in cancer

Authors: Stefan K. Zöllner, Claudia Rössig, Jeffrey A. Toretsky

Published in: Cancer and Metastasis Reviews | Issue 3/2015

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Abstract

Patients afflicted with synovial sarcoma share the fate of other translocation positive sarcomas; the driver mutation for this cancer is known, yet no means to target the fusion protein SS18-SSX directly exist. Current chemotherapeutic regimens are minimally beneficial, particularly in patients with metastatic disease. SS18-SSX putatively promotes its oncogenic activity through protein-protein interactions that alter genetic programs through chromatin remodeling. This review discusses the functional protein network of SS18-SSX, both wild-type and fusion protein, considers its intrinsically disordered nature, and provides insights into potential therapeutic strategies. A comprehensive overview of the clinical characteristics reveals the need for newly targeted therapeutics based upon oncogenic transformation by the fusion protein SS18-SSX. The wild-type, non-fused proteins SS18 and SSX are presented including their molecular structure and biological function with regard to protein-protein interactions. The interactions of the wild-type proteins inform the oncogenic changes of the fusion protein. The SS18-SSX fusion protein and its protein interactions are described and evaluated for their biological consequences that lead to oncogenesis. This review illustrates the key protein interactions of SS18-SSX that may qualify as primary targets for small molecule-based disruption leading to the development of SS18-SSX-specific drugs. These novel targeted therapeutics may provide a specificity that ultimately improves survival while reducing morbidity of patients with synovial sarcoma.
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Metadata
Title
Synovial sarcoma is a gateway to the role of chromatin remodeling in cancer
Authors
Stefan K. Zöllner
Claudia Rössig
Jeffrey A. Toretsky
Publication date
01-09-2015
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 3/2015
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-015-9575-z

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