Diagnostic Strategies and Treatment for Ewing’s Sarcoma

Abstract

Ewing's sarcoma is an enigmatic malignancy of progenitor cell origin, driven by transcription factor oncogenic fusions. About 85% of ESFT cases harbor the t(11;22) translocation and express the fusion protein EWS-FLI. Both bone marrow-derived human Mesenchymal stem cells and Neural crest stem cells are permissive for EWS-FLI1 expression that initiates transition to ESFT-like cellular phenotype. Diagnosis of Ewing's tumor is based on pathologic and molecular findings. The hypoxia enhances the malignancy of ESFT invasive capacity. An ALDH high subpopulation of Ewing's sarcoma cells, capable of self-renewal, tumor initiation and resistant to chemotherapy in vitro, are not resistant to YK-4-279. Intensive high-dose chemotherapy followed by stem-cell reconstitution was used for ESFT patients in second remission. Plerixafor in combination with G-CSF is an effective enhance stem cell mobilization regimen for stem cell collection with lowest success rate in patients with neuroblastoma. The ESFT-derived antigens EZH2(666) and CHM1(319) are suitable targets for protective allo-restricted human CD8(+) T-cell responses against non-immunogenic ESFT. Primitive neuroectodermal features and MSC origin are both compatible with G(D2) aberrant expression and explore G(D2) immune targeting in ESFT.

Functional Interactions in Transcription and Splicing of Ewing’s Sarcoma

“…ESFTs have high propensity to metastasize in bone, bone marrow, and lung. ESFTs are aggressive round cell tumors of putative stem cell origin, for which prognostic biomarkers and novel treatments are needed [2,3]. ESFTs are chemotherapy-sensitive cancers, and even patients with metastatic disease commonly achieve remission.…”