化疗、放疗、分子靶向治疗Ewing肉瘤的研究进展

Advances in chemotherapy and radiotherapy combined with molecular targeted therapy for Ewing＇s sarcoma

Ewing肉瘤是一种好发于儿童及青少年具有高度侵袭性的骨与软组织肿瘤；依靠新辅助化疗、手术及放疗等多途径联合治疗，Ewing肉瘤患者的预后及生活质量得到了明显的改善。然而，近20多年来Ewing肉瘤的治疗进入了平台期，患者的五年生存率维持在55％-75％。肿瘤的多发转移及术后复发是Ewing肉瘤患者预后差，甚至死亡的主要原因。化疗、放疗及分子靶向治疗仍是目前治疗Ewing肉瘤的主要方法。抗肿瘤药物的毒副作用、耐药性及组合方案的使用等问题一直困扰着临床工作者。对于如何提高化疗药物疗效并降低毒副反应，国内及欧美国家已针对Ewing肉瘤局部控制或复发转移的患者开展了多学科、多中心临床研究。放疗作为治疗Ewing肉瘤重要的辅助手段，治疗后患者常会出现一系列并发症，包括局部损伤或二次肿瘤的风险。因此，放疗的适应证及术前、术后放疗时机的选择还需进一步明确。目前，虽然已经发现Ewing肉瘤中存在特异性染色体易位及其易位融合基因EWS／FLI1的表达，但导致肿瘤复发及转移的具体机制仍不清楚。分子靶向治疗能通过调控EWS／FLI1上游或下游的靶向基因来抑制肿瘤的发生及发展。总之，了解Ewing肉瘤的治疗现状、多中心临床试验的成果及基因学研究理论将有助于设计新的生物疗法，从而建立个体化治疗的模式。本文就目前针对Ewing肉瘤化疗、放疗、分子靶向治疗及免疫治疗的研究进展作一综述。

Ewing＇s sarcoma is a kind of bone and soft tissue tumor which is highly invasive and mainly occurres in children and adolescents. In recent years, combined chemotherapy, surgery and radiation therapy in treatment of Ewing＇s sarcoma, patients＇ prognosis and life quality have been significantly improved. However, over the past 20 years, the treatment of Ewing＇s sarcoma entered the platform period. The 5-year overall survival rate remained at 55%-75%. Multiple metastasis and recurrence are the main factors of poor prognosis and death. Chemotherapy, radiotherapy and molecular targeted therapy are still the main methods for the treatment of Ewing sarcoma. The side effects, drug resistance and the use of the combination regimen of antitumor drugs have been plaguing the clinical workers. In order to improve the efficacy of chemotherapy drugs and reduce the toxic side effects, Multi-disciplinary and multi-center clinical studies on Ewing＇s sarcoma patients who suffered from local control or recurrence have been launched by Domestic and European and American countries. As an important supplementary mean for the treat- ment of Ewing＇s sarcoma, patients often appear a series of complications after radiotherapy, including the risk of local damage or secondary tumors. Therefore, it is necessary to further clarify the indications of radiotherapy and the timing of preoperative and postoperative radiotherapy. The specific chromosome translocation and the expression of the fusion gene EWS/FLI 1 have been found in Ewing sarcoma. Nevertheless, the mechanisms that drive tumor relapse and metastasis remain unknown. Molecular targeted therapy can be used to inhibit tumorigenesis and progression by regulating the upstream or downstream target genes of EWS/ FLI1. In conclusion understanding of the current treatment status of Ewing＇s sarcoma, results of multi-center clinical trials and theory of genomies research will contribute to the design of new biological therapies so as to establish individualized treatment modalities. In this paper, we present a review on the progress of Ewing sarcoma chemotherapy, radiotherapy, molecular targeted therapy and immunotherapy.