GSK3-beta as a candidate therapeutic target in soft tissue sarcomas
| Autor: | L. Cavalcante, R. Perret, Valérie Velasco, F. Giles, Vanessa Chaire, Antoine Italiano, Stéphanie Verbeke, Elodie Richard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
medicine.medical_specialty medicine.medical_treatment Apoptosis Inhibitor of apoptosis 9-ING-41 Mice In vivo GSK-3 Internal medicine Cell Line Tumor medicine Animals Humans Diseases of the blood and blood-forming organs Molecular Biology Letter to the Editor Protein Kinase Inhibitors RC254-282 Chemotherapy Hematology Glycogen Synthase Kinase 3 beta business.industry Soft tissue sarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sarcoma Soft tissue sarcomas medicine.disease XIAP Oncology Cancer research RC633-647.5 business Glycogen synthase kinase 3β |
| Zdroj: | Journal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-5 (2021) Journal of Hematology & Oncology |
| ISSN: | 1756-8722 |
| Popis: | Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3β (GSK-3β) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3β gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-021-01215-x. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|