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Biomedicines
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Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches
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Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 June 2025) | Viewed by 8156

Special Issue Editor

Dr. Ming-Ming Lee

E-Mail Website
Guest Editor
Department of Food Nutrition and Health Biotechnology, Asia University, Taichung City 41354, Taiwan
Interests: pharmacology of traditional Chinese medicine; neuroscience and brain cell culture; nutritional therapy in traditional Chinese medicine; cancer research and therapeutics; health promotion and aging

Special Issue Information

Dear Colleagues,

For this Special Issue, we welcome submissions focusing on, but not limited to, the following topics in glioblastoma research:

  1. Immunotherapy: Researchers are exploring ways to harness the immune system to combat GBM, for example, by using ultrasound technology to penetrate the blood–brain barrier and delivering chemotherapy drugs and immune checkpoint inhibitors into the brain to enhance the immune system's ability to recognize and attack cancer cells.
  2. Advanced radiotherapy techniques: Techniques such as proton beam therapy offer precise radiation treatment that effectively destroys cancer cells while minimizing damage to healthy tissues. This approach has shown potential in extending the survival of elderly GBM patients.
  3. Tumor microenvironment research: Researchers are delving into the interactions within the tumor microenvironment, particularly between tumor stem cells and mesenchymal stem cells. These studies reveal how tumor cells gain chemotherapy resistance through metabolic reprogramming and explore new methods to block these processes.
  4. Novel drugs and combination therapies: Researchers are developing new drugs and combination therapies to overcome resistance to existing treatments, for instance, by using small-molecule drugs to bypass conventional chemotherapy resistance mechanisms and combining them with existing therapies to enhance treatment efficacy.

Dr. Ming-Ming Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioblastoma stem cells (GSCs)
  • temozolomide (TMZ)
  • tumor microenvironment
  • resistance
  • novel therapeutic approaches

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Published Papers (3 papers)

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Research

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9 pages, 545 KB  
Article
Sex-Related Differences in Glioblastoma: A Single-Center Retrospective Cohort Study
by Chiara Prosperetti, Meltem Yenigün, Alberto Pagnamenta, Payam Tabaee Damavandi, Giulio Disanto, Francesco Marchi, Vittoria Espeli, Barbara Muoio, Paolo Spina, Gianfranco Pesce and Pamela Agazzi
Biomedicines 2025, 13(7), 1715; https://doi.org/10.3390/biomedicines13071715 - 14 Jul 2025
Viewed by 1054
Abstract
Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the [...] Read more.
Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the underlying reasons for these differences remain poorly understood. Potential contributors include hormonal influences, sex-specific risk factors, and treatment disparities. Understanding these differences is critical for optimizing personalized treatment strategies. Methods: We conducted a retrospective analysis of patients with gliomas from a neuro-oncological database, with a primary focus on GB cases. Variables collected included sex, age, tumor type, molecular biomarker, and treatment modalities. The primary objective was to assess sex-based differences in tumor characteristics and outcomes, while the secondary objective was to identify predictors of time to progression and mortality. Results: The cohort comprised 125 GB, 48 astrocytomas, and 16 oligodendrogliomas, with no significant sex-based differences in age or tumor type distribution. Among GB patients, multifocality was more prevalent in females (14% vs. 8%; p = 0.01); also, EGFR amplification was more frequent in females (25.5% vs. 52.5%; p = 0.007). Males received chemotherapy (80% vs. 63%; p = 0.04) and radiotherapy (84% vs. 67%; p = 0.03) more frequently than females. Survival was positively associated with MGMT methylation (p = 0.002) and negatively associated with TERT mutation (p = 0.01). Multivariable analysis identified TERT mutation as a predictor of increased mortality (HR = 4.1; 95% CI: 1.2–14; p = 0.025), while multifocality predicted both mortality (HR = 2.3; 95% CI: 1.3–3.9; p = 0.003) and reduced time to progression (HR = 3.3; 95% CI: 1.02–10.6; p = 0.04). Conclusions: This study underscores the importance of sex and molecular profiling in GB management, revealing distinct patterns in tumor characteristics and treatment administration between males and females. Our findings advocate for the integration of sex-specific considerations and molecular profiling into clinical decision-making to improve outcomes for GB patients. Full article
(This article belongs to the Special Issue Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches)
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Review

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27 pages, 415 KB  
Review
Radiotherapy in Glioblastoma Multiforme: Evolution, Limitations, and Molecularly Guided Future
by Castalia Fernández, Raquel Ciérvide, Ana Díaz, Isabel Garrido and Felipe Couñago
Biomedicines 2025, 13(9), 2136; https://doi.org/10.3390/biomedicines13092136 - 1 Sep 2025
Cited by 1 | Viewed by 4537
Abstract
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) [...] Read more.
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article
(This article belongs to the Special Issue Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches)
34 pages, 1654 KB  
Review
Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches
by Anatevka Ribeiro, Gianna Fote, Alexander Himstead, Michelle Zheng, Emma Elliott, Sara Mae Smith, Jerry Lou and Carlen A. Yuen
Biomedicines 2025, 13(8), 1963; https://doi.org/10.3390/biomedicines13081963 - 12 Aug 2025
Cited by 1 | Viewed by 2163
Abstract
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Despite the current standard of care therapy, including maximal surgical resection, chemoradiation, and tumor-treating fields, prognosis remains poor. Therapeutic failure is driven by an immunosuppressive tumor microenvironment, poor drug penetration across [...] Read more.
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Despite the current standard of care therapy, including maximal surgical resection, chemoradiation, and tumor-treating fields, prognosis remains poor. Therapeutic failure is driven by an immunosuppressive tumor microenvironment, poor drug penetration across the blood–brain barrier, and robust resistance mechanisms. Epigenetic alterations further compound treatment resistance by enhancing DNA repair and promoting survival pathways. Molecular profiling has identified key prognostic and predictive biomarkers. Gene expression analyses have delineated GBM subtypes, each with distinct molecular features and therapeutic vulnerabilities that hinder successful clinical translation. This review integrates the pathophysiological, diagnostic, and therapeutic landscape of GBM to inform of future strategies for improved patient outcomes. Full article
(This article belongs to the Special Issue Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches)
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