Yu Hongjiu, Ge Yonggui, Guo Lianying, Huang Lin
Department of Pathophysiology, Dalian Medical University, Dalian, Liaoning, P.R. China.
Department of VIP, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China.
Oncotarget. 2017 Jan 17;8(3):5523-5539. doi: 10.18632/oncotarget.12566.
Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise. There has also been increasing interest in the immune responses of ES patients. Immunotherapies using T cells, NK cells, cancer vaccines and monoclonal antibodies have been considered for ES, especially for recurrent patients. Because understanding the pathogenesis of ES is extremely important for the development of novel treatments, this review focuses on the mechanisms and functions of targeted therapies and immunotherapies in ES. It is anticipated that integrating the knowledge obtained from basic research and translational and clinical studies will lead to the development of novel therapeutic strategies for the treatment of ES.
尤因肉瘤（ES）是儿童和青年中一种具有高度侵袭性和转移性的肿瘤，由尤因肉瘤断点区域1（EWSR1）基因与转录因子FLI1基因之间的染色体融合所致。ES采用包括化疗、手术和放疗在内的标准治疗方法。尽管原发性ES的5年生存率有所提高，但发生转移或复发的ES患者的生存率仍然很低。最近在临床前和临床环境中已鉴定并研究了ES中的几个新分子靶点，靶向受体酪氨酸激酶（RTK）、融合蛋白EWS-FLI1和mTOR的功能已显示出前景。对ES患者的免疫反应也越来越感兴趣。使用T细胞、NK细胞、癌症疫苗和单克隆抗体的免疫疗法已被考虑用于ES，特别是对于复发患者。由于了解ES的发病机制对于开发新疗法极为重要，本综述重点关注ES中靶向治疗和免疫治疗的机制及功能。预计整合从基础研究以及转化和临床研究中获得的知识将推动开发治疗ES的新治疗策略。
