Synovial sarcoma is a gateway to the role of chromatin remodeling in cancer.
Synovial sarcoma is a gateway to the role of chromatin remodeling in cancer.
复制标题
滑膜肉瘤是了解染色质重塑在癌症中的作用的途径。
DOI：
10.1007/s10555-015-9575-z
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Toretsky,JeffreyA
中科院分区：
文献类型：
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作者：
Zöllner,StefanK;Rössig,Claudia;Toretsky,JeffreyA
患有滑膜肉瘤的患者与其他易位阳性肉瘤的命运相同;这种癌症的驱动突变是已知的，但不存在直接靶向融合蛋白SS 18-SSX的方法。目前的化疗方案是最低限度的有益的，特别是在转移性疾病的患者。SS 18-SSX蛋白质通过蛋白质-蛋白质相互作用促进其致癌活性，蛋白质-蛋白质相互作用通过染色质重塑改变遗传程序。本文综述了SS 18-SSX的功能蛋白网络，包括野生型和融合蛋白，考虑其内在的无序性，并提供了潜在的治疗策略的见解。对临床特征的全面概述揭示了对基于融合蛋白SS 18-SSX的致癌转化的新靶向治疗的需要。野生型，非融合蛋白SS 18和SSX，包括其分子结构和生物学功能方面的蛋白质-蛋白质相互作用。野生型蛋白的相互作用告知融合蛋白的致癌变化。SS 18-SSX融合蛋白及其蛋白质相互作用的描述和评估其生物学后果，导致肿瘤发生。这篇综述阐述了SS 18-SSX的关键蛋白质相互作用，这些相互作用可能有资格作为基于小分子的破坏的主要靶点，从而导致SS 18-SSX特异性药物的开发。这些新的靶向治疗可能提供特异性，最终提高生存率，同时降低滑膜肉瘤患者的发病率。
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.