Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?
: Söderberg-Naucler, Cecilia; Pantalone, Mattia R.; Stragliotto, Giuseppe; Bartek, Jiri
Publisher: The Royal Society
: 2025
Philosophical Transactions B: Biological Sciences
: 20240403
: 380
: 1938
: 0962-8436
: 1471-2970
DOI: https://doi.org/10.1098/rstb.2024.0403
: https://doi.org/10.1098/rstb.2024.0403
: https://research.utu.fi/converis/portal/detail/Publication/505224094
Glioblastoma is the most common and aggressive primary malignant brain tumour in adults, with limited treatment options despite years of research. Since the 2005 introduction of the current standard of care, hundreds of clinical trials have failed to deliver significant breakthroughs. In 2002, human cytomegalovirus (HCMV) was detected in 100% of glioblastoma tumours. Although its role in cancer remains debated, and HCMV is not classified as an oncovirus, numerous studies have reported high viral prevalence in glioblastoma. HCMV can induce all 10 'hallmarks of cancer' and has been shown to modify both tumour cell behaviour and the microenvironment, which may enhance tumour growth and promote immune evasion. The association between HCMV and poor glioblastoma prognosis has generated increasing interest in targeting the virus therapeutically. Our clinical studies suggest that adding antiviral treatment to standard care may improve survival in both primary and recurrent glioblastoma. Moreover, an mRNA-based HCMV pp65 dendritic cell vaccine has shown preliminary indications of a potential survival benefit in early phase studies. Future research should prioritize clarifying HCMV's role in glioblastoma and rigorously evaluating antiviral and immunotherapeutic strategies in randomized clinical trials.This article is part of the theme issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'.
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This work was supported by grants from the Lundbeck Foundation (grant R453-2024-326), the Research Council of Finland’s Flagship InFLAMES (337530 and 357910), the Swedish Medical Research Council (2016-00484, 2019-01736, 2022-02724), the Family Ehrling Persson's Foundation, the Sten A. Olssons Foundation, the BILTEMA Foundation, the Family of Jochnick Foundation, the Danish Cancer Society (R322-A17482), the Novo Nordisk Foundation (0060590), the Swedish Research Council (VR-MH 2014-46602-117891-30), Cancerfonden (170176), the Foundation Cure Cancer through a private donation from Professor Erna Möller, the Grant Agency of the Czech Ministry of Health (NU21-03-00195), the Danish National Research Foundation (DNRF 125), the Sigrid Juselius Foundation (8167), the Cancer Foundation Finland (69-7706) and the Finnish Research Impact Foundation (687).
