下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Genetic and Molecular Heterogeneity of Synovial Sarcoma and Associated Challenges in Therapy.
Genetic and Molecular Heterogeneity of Synovial Sarcoma and Associated Challenges in Therapy.
滑膜肉瘤(SS)是儿童软组织肉瘤(STS)中最常见的类型之一,在成人中则远为少见。
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。其特征性染色体易位为SS18-SSX,并伴随相关信号改变。然而,SS中的其他遗传和表观遗传异常未必与SS18-SSX事件相关;这些异常更为零散,与预后和治疗反应的相关性也较差。目前,滑膜肉瘤的靶向治疗药物选择有限;对于局限性肿瘤,手术切除仍是主要治疗方式,并可辅以新辅助或辅助化疗及放疗。了解不同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日益重要。新型治疗策略包括免疫疗法(如针对NY-ESO-1、MAGE4或PRAME的TCR-T细胞疗法,以及免疫检查点抑制剂)、表观遗传调节剂(HDAC抑制剂、EZH2抑制剂和BRD抑制剂),以及新型或经重新定位使用的受体酪氨酸激酶抑制剂。本综述旨在总结滑膜肉瘤的遗传和表观遗传图谱,并探讨开发新型诊断与治疗方法的潜在方向。
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.
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