Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy
BackgroundGlioblastoma (GBM) is the deadliest form of brain cancer, impacting both adults and children, marked by exceptionally high morbidity and mortality rates, even with current standard treatments such as surgery, radiation therapy, and chemotherapy. Therefore, there is a pressing need for new...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1451156/full |
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| author | Julia Uffenorde Mehran Hariri Eleftherios Papalanis Annika Staffas Josefine Berg Bo Stenerlöw Hanna Berglund Christer Malmberg Diana Spiegelberg Diana Spiegelberg |
| author_facet | Julia Uffenorde Mehran Hariri Eleftherios Papalanis Annika Staffas Josefine Berg Bo Stenerlöw Hanna Berglund Christer Malmberg Diana Spiegelberg Diana Spiegelberg |
| author_sort | Julia Uffenorde |
| collection | DOAJ |
| description | BackgroundGlioblastoma (GBM) is the deadliest form of brain cancer, impacting both adults and children, marked by exceptionally high morbidity and mortality rates, even with current standard treatments such as surgery, radiation therapy, and chemotherapy. Therefore, there is a pressing need for new therapeutic strategies to improve survival and reduce treatment side effects. In this study, we investigated the effect of HSP90 inhibition in combination with radiotherapy in established and patient-derived glioblastoma cell lines.MethodsPotential radiosensitizing effects of the HSP90 inhibitor Onalespib were studied in XTT and clonogenic survival assays as well as in tumor-mimicking multicellular spheroid models. Further, migration capacity and effects on protein expression were studied after exposure to Onalespib and radiation using Proximity Extension Assay analysis.ResultsHSP90 inhibition with Onalespib synergistically enhanced the radiosensitivity of glioblastoma cells grown in 2D and 3D models, resulting in increased cell death, reduced migration capacity and activation of the apoptotic signaling pathway. The proteomic analysis of glioblastoma cells treated with Onalespib, radiation, and their combination revealed significant alterations in protein expression profiles, involved in growth signaling, immune modulation pathways and angiogenesis. Moreover, the combination treatment indicated potential for enhancing cell cycle arrest and apoptosis, suggesting promising anti-tumor effects.ConclusionThese findings demonstrate that HSP90 inhibition may be a promising strategy to enhance the efficacy of radiotherapy in the treatment of GBM, potentially leading to improved outcomes for patients battling this challenging disease. |
| format | Article |
| id | doaj-art-c9c22414adda4b2d8825eaa682fd715d |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-c9c22414adda4b2d8825eaa682fd715d2025-01-30T06:22:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011510.3389/fonc.2025.14511561451156Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapyJulia Uffenorde0Mehran Hariri1Eleftherios Papalanis2Annika Staffas3Josefine Berg4Bo Stenerlöw5Hanna Berglund6Christer Malmberg7Diana Spiegelberg8Diana Spiegelberg9Department of Surgical Sciences, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Medical Sciences, Uppsala University, Uppsala, SwedenDepartment of Surgical Sciences, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenBackgroundGlioblastoma (GBM) is the deadliest form of brain cancer, impacting both adults and children, marked by exceptionally high morbidity and mortality rates, even with current standard treatments such as surgery, radiation therapy, and chemotherapy. Therefore, there is a pressing need for new therapeutic strategies to improve survival and reduce treatment side effects. In this study, we investigated the effect of HSP90 inhibition in combination with radiotherapy in established and patient-derived glioblastoma cell lines.MethodsPotential radiosensitizing effects of the HSP90 inhibitor Onalespib were studied in XTT and clonogenic survival assays as well as in tumor-mimicking multicellular spheroid models. Further, migration capacity and effects on protein expression were studied after exposure to Onalespib and radiation using Proximity Extension Assay analysis.ResultsHSP90 inhibition with Onalespib synergistically enhanced the radiosensitivity of glioblastoma cells grown in 2D and 3D models, resulting in increased cell death, reduced migration capacity and activation of the apoptotic signaling pathway. The proteomic analysis of glioblastoma cells treated with Onalespib, radiation, and their combination revealed significant alterations in protein expression profiles, involved in growth signaling, immune modulation pathways and angiogenesis. Moreover, the combination treatment indicated potential for enhancing cell cycle arrest and apoptosis, suggesting promising anti-tumor effects.ConclusionThese findings demonstrate that HSP90 inhibition may be a promising strategy to enhance the efficacy of radiotherapy in the treatment of GBM, potentially leading to improved outcomes for patients battling this challenging disease.https://www.frontiersin.org/articles/10.3389/fonc.2025.1451156/fullCNS tumorssynergyheat shock proteinradiotherapycombination therapyproteomics |
| spellingShingle | Julia Uffenorde Mehran Hariri Eleftherios Papalanis Annika Staffas Josefine Berg Bo Stenerlöw Hanna Berglund Christer Malmberg Diana Spiegelberg Diana Spiegelberg Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy Frontiers in Oncology CNS tumors synergy heat shock protein radiotherapy combination therapy proteomics |
| title | Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy |
| title_full | Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy |
| title_fullStr | Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy |
| title_full_unstemmed | Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy |
| title_short | Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy |
| title_sort | enhancing glioblastoma therapy unveiling synergistic anticancer effects of onalespib radiotherapy combination therapy |
| topic | CNS tumors synergy heat shock protein radiotherapy combination therapy proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1451156/full |
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