AccScience Publishing / GPD / Online First / DOI: 10.36922/GPD025340062
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REVIEW ARTICLE

Instability as a source of diversity in glioblastoma

Isabele Pagani Pavan1 ,  Bianca Paulino Campanharo1 ,  Felipe Ataides Mion1 ,  Flávio dos Santos Alvarenga1 ,  Matheus Correia Casotti1 ,  Lorena Souza Castro Altoé1 ,  Iúri Drumond Louro1 ,  Débora Dummer Meira1*
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1 Center for Human and Molecular Genetics, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil
GPD, 025340062 https://doi.org/10.36922/GPD025340062
Received: 18 August 2025 | Revised: 23 October 2025 | Accepted: 5 November 2025 | Published online: 20 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Glioblastoma (GB) is one of the most aggressive and prevalent primary brain tumors in adults, accounting for approximately 15% of all brain tumors and 78% of all malignant brain tumors. This article aims to review the current understanding of GB, with a particular focus on the role of tumor heterogeneity in treatment resistance, the underexplored role of ploidy variation in GB biology, and the emerging and individualized therapeutic strategies designed to enhance treatment efficacy. A narrative review of the literature was conducted, synthesizing recent findings on GB development, diagnosis, and therapeutic innovations. Special attention was given to studies that discuss: molecular and cellular characteristics of GB; novel therapeutic approaches, including targeted inhibitors, combination therapies, and virotherapy; the clinical significance of inter- and intratumoral heterogeneity. The results indicate that GB’s resistance to therapy is closely linked to its pronounced heterogeneity, both at the inter- and intratumoral levels. Variability in ploidy among tumor cells has emerged as a potential contributor to treatment failure, yet it remains insufficiently investigated. Promising therapeutic developments include inhibitors targeting specific proteins or signaling pathways, synergistic combination treatments, and oncolytic virotherapy. Although these approaches show potential, most remain in early-stage research or clinical trials. The review underscores the importance of precision medicine in overcoming the barriers posed by GB’s heterogeneity. While emerging therapies are promising, the development of individualized, patient-specific strategies remains essential.

Keywords
Cancer
Ploidy variation
Polyploidy
Multinucleation
Funding
None.
Conflict of interest
Iúri Drumond Louro is an Editorial Board Member of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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