Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, Moscow 115478, Russia.
Oncology Department, Ryazan State Medical University Named after Academician I.P. Pavlov, Ministry of Health of Russia, Ryazan 390026, Russia.
Cells. 2024 Oct 14;13(20):1695. doi: 10.3390/cells13201695.
Synovial sarcoma (SS) is one of the most common types of pediatric soft tissue sarcoma (STS) being far less frequent in adults. This STS type is characterized by one specific chromosomal translocation SS18-SSX and the associated changes in signaling. However, other genetic and epigenetic abnormalities in SS do not necessarily include SS18-SSX-related events, but abnormalities are more sporadic and do not correlate well with the prognosis and response to therapy. Currently, targeted therapy for synovial sarcoma includes a limited range of drugs, and surgical resection is the mainstay treatment for localized cancer with adjuvant or neoadjuvant chemotherapy and radiotherapy. Understanding the molecular characteristics of synovial sarcoma subtypes is becoming increasingly important for detecting new potential targets and developing innovative therapies. Novel approaches to treating synovial sarcoma include immune-based therapies (such as TCR-T cell therapy to NY-ESO-1, MAGE4, PRAME or using immune checkpoint inhibitors), epigenetic modifiers (HDAC inhibitors, EZH2 inhibitors, BRD disruptors), as well as novel or repurposed receptor tyrosine kinase inhibitors. In the presented review, we aimed to summarize the genetic and epigenetic landscape of SS as well as to find out the potential niches for the development of novel diagnostics and therapies.
滑膜肉瘤（SS）是儿童软组织肉瘤（STS）中最常见的类型之一，在成人中则少见得多。这种 STS 类型的特征是存在一种特定的染色体易位 SS18-SSX 以及相关的信号转导变化。然而，SS 中的其他遗传和表观遗传异常不一定包括 SS18-SSX 相关事件，但异常更为散在，与预后和对治疗的反应相关性不佳。目前，滑膜肉瘤的靶向治疗包括有限范围的药物，手术切除是局限性癌症的主要治疗方法，辅以辅助或新辅助化疗和放疗。了解滑膜肉瘤亚型的分子特征对于发现新的潜在靶点和开发创新疗法变得越来越重要。滑膜肉瘤的新治疗方法包括免疫疗法（如针对 NY-ESO-1、MAGE4、PRAME 的 TCR-T 细胞疗法，或使用免疫检查点抑制剂）、表观遗传修饰剂（组蛋白去乙酰化酶抑制剂、EZH2 抑制剂、BRD 破坏剂），以及新型或重新利用的受体酪氨酸激酶抑制剂。在本次综述中，我们旨在总结 SS 的遗传和表观遗传景观，并找出开发新型诊断和治疗方法的潜在途径。
