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Παρασκευή 6 Απριλίου 2018

Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Andrea A. Hayes-Jordan, Xiao Ma, Brian A. Menegaz, Salah-Eddine Lamhamedi-Cherradi, Charles V. Kingsley, Jalen A. Benson, Pamela E. Camacho, Joseph A. Ludwig, Cynthia R. Lockworth, Gloria E. Garcia, Suzanne L. Craig
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.



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