Ewing Sarcoma

P2/3, N=437, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting | Initiation date: Jul 2026 --> Nov 2025

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting | N=46 --> 90

This case highlights the diagnostic complexities of round cell sarcoma of bone, which can mimic other benign bone lesions. It underscores the importance of multidisciplinary evaluation, genetic testing, and timely oncological intervention to improve patient outcomes.

Next-Generation Sequencing (NGS) revealed EWSR1::FLI1 rearrangement in all three tested PCES cases (100%). In conclusion, the accurate diagnosis of PCES requires a comprehensive approach, integrating detailed morphologic assessment with immunohistochemical studies and potentially cytogenetics/molecular assays.

This proof-of-concept study demonstrates that DNA binding proteins with pioneering transcription factor activity, such as EWSR1::FLI1, can be relocalized on chromatin to induce expression of repressed genes. Insights herein will guide the development of future bivalent molecules that rewire DNA binding transcriptional machinery.

So, it is highly probable that a chromosomal translocation and the subsequent formation of the EWSR1-ETS fusion protein cause the genomic alterations in EwS. This indicates that targeted therapy should be directed against the CNA and LOH biology caused by the fusion protein.

We have previously reported that WNT974, a selective Porcn inhibitor, delays the onset of metastases in three different xenograft models of Ewing sarcoma with no effect on primary tumor growth, suggesting a specific role of the drug in metastasis...Crispr-Cas9 editing of Wnt5a results in an inability of the cells to migrate with a global lack of filamentous actin in the cell cytoskeleton. These findings suggest that a Wnt5a-dependent signaling pathway drives the cytoskeletal changes and cell adhesion molecule changes necessary for early steps of migration in the metastatic cascade.

The predicted heatmap graph also highlighted the significance of hsa-let-7a in various cellular signaling pathways, which may be interconnected with Ewing sarcoma, making it a potential therapeutic target. Together, this study offers computational insights that highlight hsa-let-7a as a promising therapeutic candidate for Ewing sarcoma, based on miRNA-driven predictive modeling.

Exposing EwS cells to the Menin inhibitor VTP50469 (revumenib) inhibited expression of MYC targets and co-immunoprecipitation studies detected Menin:MYC interactions that were partially disrupted by the drug. Metastatic colonization of disseminated EwS cells in vivo was significantly inhibited in mice fed VTP50469 chow. Together these findings implicate Menin as a mediator of EwS metastasis and suggest that Menin inhibitors warrant investigation as novel therapeutics for patients with high-risk disease.

DNA methylation profiling successfully classified gynecologic neuroectodermal tumors as known CNS tumor or sarcoma entities. Epigenetic and exomic studies suggest a male genome and increased maternal allelic contribution in CNS-like tumors, suggesting development via conception or chimerism.

This reagent will provide the research community with valuable tools for further biochemical and genomic interrogation of the oncogenic activity of EWS::FLI1 in ES.