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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Neuro-Oncology and Neurosurgical Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1451156
This article is part of the Research Topic Advances in Brain Tumor Therapy View all 10 articles

Enhancing Glioblastoma Therapy: Unveiling Synergistic Anticancer Effects of Onalespib -Radiotherapy Combination Therapy

Provisionally accepted
Julia Uffenorde Julia Uffenorde 1Mehran Hariri Mehran Hariri 2Eleftherios Papalanis Eleftherios Papalanis 2Annika Staffas Annika Staffas 2Josefine Berg Josefine Berg 2Bo Stenerlöw Bo Stenerlöw 2Hanna Berglund Hanna Berglund 2Christer Malmberg Christer Malmberg 3Diana Spiegelberg Diana Spiegelberg 1,2*
  • 1 Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
  • 2 Department of Immunology, Genetics and Pathology, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
  • 3 Department of Medical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden

The final, formatted version of the article will be published soon.

    Glioblastoma (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.Potential 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. HSP90 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.These 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.

    Keywords: CNS tumors1, synergy2, heat shock protein3, radiotherapy4, combination therapy5, Proteomics6, Proximity extension assay7

    Received: 18 Jun 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Uffenorde, Hariri, Papalanis, Staffas, Berg, Stenerlöw, Berglund, Malmberg and Spiegelberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Diana Spiegelberg, Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, SE-751 85, Uppsala, Sweden

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