Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor
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 liv...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558617303561 |
| _version_ | 1818678519861870592 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Andrea A. Hayes-Jordan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T09:16:34Z |
| format | Article |
| id | doaj.art-20dc9cf4609a48779730b00ad5c9d919 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-17T09:16:34Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-20dc9cf4609a48779730b00ad5c9d9192022-12-21T21:54:57ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862018-05-01205524532Efficacy of ONC201 in Desmoplastic Small Round Cell TumorAndrea A. Hayes-Jordan0Xiao Ma1Brian A. Menegaz2Salah-Eddine Lamhamedi-Cherradi3Charles V. Kingsley4Jalen A. Benson5Pamela E. Camacho6Joseph A. Ludwig7Cynthia R. Lockworth8Gloria E. Garcia9Suzanne L. Craig10Division of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 1484, Houston, TX, USA; Address all correspondence to: Andrea A. Hayes-Jordan, University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, 1400 Pressler St., Unit 1484, Houston, TX 77030.Division of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 1484, Houston, TX, USADivision of Sarcoma Medical Oncology-Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 1952, Houston, TX, USADivision of Sarcoma Medical Oncology-Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 1952, Houston, TX, USADepartment of Imaging Physics-Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 1902, Houston, TX, USADivision of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 1484, Houston, TX, USADepartment of Pediatrics-Patient Care, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 0087, Houston, TX, USADepartment of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 0450, Houston, TX, USADepartment of Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 0063, Houston, TX, USADepartment of Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 0063, Houston, TX, USADepartment of Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit, 0063, Houston, TX, USADesmoplastic 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.http://www.sciencedirect.com/science/article/pii/S1476558617303561 |
| spellingShingle | 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 Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor Neoplasia: An International Journal for Oncology Research |
| title | Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor |
| title_full | Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor |
| title_fullStr | Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor |
| title_full_unstemmed | Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor |
| title_short | Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor |
| title_sort | efficacy of onc201 in desmoplastic small round cell tumor |
| url | http://www.sciencedirect.com/science/article/pii/S1476558617303561 |
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