Novel Targeted Therapeutic Strategies for Ewing Sarcoma

SIMPLE SUMMARY: Ewing sarcoma is an uncommon cancer that arises in mesenchymal tissues and represents the second most widespread malignant bone neoplasm after osteosarcoma in children. Therapy has increased the 5-year survival rate in the last 40 years, although the recurrence rate has remained high. There is an immediate and unmet need for the development of novel Ewing sarcoma therapies. We offer new prospective targets for the therapy of Ewing sarcoma. The EWSR1/FLI1 fusion protein, which is identified in 85–90% of Ewing sarcoma tumors, and its direct targets are given special focus in this study. Experimantal therapy that targets multiple signaling pathways activated during ES progression, alone or in combination with existing regimens, may become the new standard of care for Ewing sarcoma patients, improving patient survival. ABSTRACT: Ewing sarcoma (ES) is an uncommon cancer that arises in mesenchymal tissues and represents the second most widespread malignant bone neoplasm after osteosarcoma in children. Amplifications in genomic, proteomic, and metabolism are characteristics of sarcoma, and targeting altered cancer cell molecular processes has been proposed as the latest promising strategy to fight cancer. Recent technological advancements have elucidated some of the underlying oncogenic characteristics of Ewing sarcoma. Offering new insights into the physiological basis for this phenomenon, our current review examines the dynamics of ES signaling as it related to both ES and the microenvironment by integrating genomic and proteomic analyses. An extensive survey of the literature was performed to compile the findings. We have also highlighted recent and ongoing studies integrating metabolomics and genomics aimed at better understanding the complex interactions as to how ES adapts to changing biochemical changes within the tumor microenvironment.