Koustas Evangelos, Sarantis Panagiotis, Karamouzis Michalis V, Vielh Philippe, Theocharis Stamatios
First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Biomolecules. 2021 Feb 26;11(3):355. doi: 10.3390/biom11030355.
Ewing Sarcoma (ES) is a rare, aggressive, and highly metastasizing cancer in children and young adults. Most ES cases carry the fusion of the Ewing Sarcoma Breakpoint Region 1 () and (Friend leukemia virus integration site 1) genes, leading to an EWS-FLI1 fused protein, which is associated with autophagy, a homeostatic and catabolic mechanism under normal and pathological conditions. Following such interesting and controversial data regarding autophagy in ES, many clinical trials using modulators of autophagy are now underway in this field. In the present review, we summarize current data and clinical trials that associate autophagy with ES. In vitro studies highlight the controversial role of autophagy as a tumor promoter or a tumor suppressor mechanism in ES. Clinical and in vitro studies on ES, together with the autophagy modulators, suggest that caution should be adopted in the application of autophagy as a therapeutic target. Monitoring and targeting autophagy in every ES patient could eliminate the need for targeting multiple pathways in order to achieve the maximum beneficial effect. Future studies are required to focus on which ES patients are affected by autophagy modulators in order to provide novel and more efficient therapeutic protocols for patients with ES based on the current autophagy status of the tumors.
尤因肉瘤（ES）是一种在儿童和青年中罕见、侵袭性强且高度转移的癌症。大多数ES病例携带尤因肉瘤断点区域1（EWSR1）和（Friend白血病病毒整合位点1，FLI1）基因的融合，导致EWS-FLI1融合蛋白，该蛋白与自噬相关，自噬是正常和病理条件下的一种稳态和分解代谢机制。鉴于ES中有关自噬的这些有趣且有争议的数据，目前该领域正在进行许多使用自噬调节剂的临床试验。在本综述中，我们总结了将自噬与ES相关联的当前数据和临床试验。体外研究突出了自噬在ES中作为肿瘤促进或肿瘤抑制机制的争议性作用。关于ES的临床和体外研究以及自噬调节剂表明，在将自噬作为治疗靶点应用时应谨慎。监测并针对每位ES患者的自噬情况，可能无需针对多种途径就能实现最大益处。未来的研究需要聚焦于哪些ES患者会受到自噬调节剂的影响，以便根据肿瘤当前的自噬状态为ES患者提供新颖且更有效的治疗方案。
