Ewing sarcoma (EwS) is a rare and predominantly pediatric malignancy of bone and soft tissue in children and adolescents. Although international collaborations have greatly improved the prognosis of most EwS, the occurrence of macrometastases or relapse remains challenging. The prototypic oncogene EWS-FLI1 acts as an aberrant transcription factor that drives the cellular transformation of EwS. In addition to its involvement in RNA splicing and the DNA damage response, this chimeric protein directly binds to GGAA repeats, thereby modifying the transcriptional profile of EwS. Direct pharmacological targeting of EWS-FLI1 is difficult because of its intrinsically disordered structure. However, targeting the EWS-FLI1 protein complex or downstream pathways provides additional therapeutic options. This review describes the EWS-FLI1 protein partners and downstream pathways, as well as the related target therapies for the treatment of EwS.
尤文肉瘤是一种罕见且主要发生于儿童和青少年的骨与软组织恶性肿瘤。尽管国际合作已极大改善了大多数尤文肉瘤患者的预后，但大转移或复发的出现仍是临床治疗难题。其原型致癌基因EWS-FLI1作为异常转录因子驱动尤文肉瘤的细胞转化。该嵌合蛋白除参与RNA剪接和DNA损伤应答外，还能直接结合GGAA重复序列，从而改变尤文肉瘤的转录特征。由于EWS-FLI1蛋白本身具有天然无序结构特性，直接药物靶向作用较为困难，但针对EWS-FLI1蛋白复合物或下游信号通路的干预为治疗提供了更多可能性。本综述系统阐述了EWS-FLI1的蛋白伴侣与下游通路，以及相关的尤文肉瘤靶向治疗策略。
肿瘤(癌症)患者之家