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:Molecular and epigenetic oncogenesis in synovial sarcoma: implications for cancer biology, diagnosis and treatment.
SS18::SSX 癌基因是滑膜肉瘤的驱动因素,这是一种侵袭性癌症,多见于年轻成人,长期预后较差。
SS18::SSX 癌基因是滑膜肉瘤的驱动因素,滑膜肉瘤是一种发生于年轻成人的侵袭性癌症,长期预后较差。在过去五年中,对滑膜肉瘤的分子、基因组和表观遗传机制的理解取得了重大进展。本综述综合了滑膜肉瘤的最新进展,包括诊断病理学、基因组分析、SS18::SSX 生物学、表观遗传失调、蛋白质组学、可靶向通路和免疫治疗。关键发现包括鉴定出罕见但具有启示意义的替代性基因融合、PRC1 和液-液相分离在 SS18::SSX 介导的肿瘤发生中的作用,以及表观遗传疗法和工程化 T 细胞疗法的开发。这些进展为改善滑膜肉瘤患者的治疗和预后带来了新希望,但在克服耐药性和确保新兴疗法的公平可及性方面仍存在挑战。
The SS18::SSX oncogene is the driver of synovial sarcoma, an aggressive cancer presenting in young adults that has poor long-term outcomes. Over the past five years, significant progress has been made in understanding the molecular, genomic, and epigenetic mechanisms underlying synovial sarcoma. This review synthesizes recent advancements in synovial sarcoma, including diagnostic pathology, genomic profiling, SS18::SSX biology, epigenetic dysregulation, proteomics, targetable pathways and immunotherapy. Key findings include the identification of rare but instructive alternative gene fusions, the roles of PRC1 and of liquid-liquid phase separation in SS18::SSX-mediated oncogenesis, and the development of epigenetic and engineered T-cell therapies. These advances offer new hope for improved treatments and outcomes in synovial sarcoma patients, though challenges remain in overcoming resistance and ensuring equitable access to emerging therapies.
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