Novel Therapeutic Strategies for Glioblastoma

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Clinical Pharmaceutics".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 7044

Special Issue Editors


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Guest Editor
Department of Neurobiology, Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
Interests: molecular neurooncology; glioblastoma; tumor microenvironment; 3D cultures; innovative anticancer drugs
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Neurobiology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
Interests: molecular neurooncology; glioblastoma; tumor microenvironment; 3D cultures; innovative anticancer drugs

E-Mail Website
Guest Editor
Department of Neurobiology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
Interests: molecular neurooncology; glioblastoma; tumor microenvironment; 3D cultures; innovative anticancer drugs

Special Issue Information

Dear Colleagues,

Adult glioblastoma is the most common and most aggressive type of primary brain cancer. It is a highly heterogenic cancer whose malignant cells are invasive and intrinsically resistant to any applied therapy. Despite numerous clinical studies that have been conducted in the last two decades, glioblastoma remains unresponsive to diverse available therapies (targeted molecular therapeutics, cellular and immune therapies, as well as alternating electrical fields). The standard procedure, dating from 2005, is surgical resection followed by radiotherapy with concomitant temozolomide chemotherapy; it has failed to prolong glioblastoma patient survival. Therefore, new therapeutic strategies that can overcome glioblastoma resistance and recurrence and improve patient survival are necessary.

This Special Issue will assemble preclinical and clinical studies of novel therapeutic strategies for glioblastoma. In addition, reviews referring to glioblastoma research and therapy will be appreciated.

Dr. Milica Pešić
Dr. Ana Podolski-Renić
Dr. Jelena Dinić
Guest Editors

Manuscript Submission Information

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Keywords

  • glioblastoma
  • novel therapeutic strategies
  • preclinical models
  • clinical studies
  • resistance to therapy
  • gene therapy
  • stem cell therapy
  • immunotherapy
  • natural compounds

Published Papers (3 papers)

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Research

16 pages, 2533 KiB  
Article
Biomolecules to Biomarkers? U87MG Marker Evaluation on the Path towards Glioblastoma Multiforme Pathogenesis
by Markéta Pokorná, Viera Kútna, Saak V. Ovsepian, Radoslav Matěj, Marie Černá and Valerie Bríd O’Leary
Pharmaceutics 2024, 16(1), 123; https://doi.org/10.3390/pharmaceutics16010123 - 18 Jan 2024
Cited by 1 | Viewed by 1033
Abstract
The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules [...] Read more.
The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules to the realm of GBM pathogenesis. Our study’s objectives were to address this preclinical issue and assess prominin-1, ICAM-1, PARTICLE and GAS5 as potential GBM diagnostic targets. The methodologies included haemoxylin and eosin staining, immunofluorescence, in situ hybridization and quantitative PCR. The findings identified that morphology correlates with malignancy in GBM patient pathology. Immunofluorescence confocal microscopy revealed prominin-1 in pseudo-palisades adjacent to necrotic foci in both animal and human GBM. Evidence is presented for an ICAM-1 association with degenerating vasculature. Significantly elevated nuclear PARTICLE expression from in situ hybridization and quantitative PCR reflected its role as a tumor activator. GAS5 identified within necrotic GBM validated this potential prognostic biomolecule with extended survival. Here we present evidence for the stem cell marker prominin-1 and the chemotherapeutic target ICAM-1 in a glioma animal model and GBM pathology sections from patients that elicited alternative responses to adjuvant chemotherapy. This foremost study introduces the long non-coding RNA PARTICLE into the context of human GBM pathogenesis while substantiating the role of GAS5 as a tumor suppressor. The validation of GBM biomarkers from cellular models contributes to the advancement towards superior detection, therapeutic responders and the ultimate attainment of promising prognoses for this currently incurable brain cancer. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies for Glioblastoma)
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22 pages, 13118 KiB  
Article
Glioblastoma Multiforme: Probing Solutions to Systemic Toxicity towards High-Dose Chemotherapy and Inflammatory Influence in Resistance against Temozolomide
by Sadia Nasir, Sadia Nazir, Rumeza Hanif and Aneela Javed
Pharmaceutics 2023, 15(2), 687; https://doi.org/10.3390/pharmaceutics15020687 - 17 Feb 2023
Cited by 6 | Viewed by 2113
Abstract
Temozolomide (TMZ), the first-line chemotherapeutic drug against glioblastoma multiforme (GBM), often fails to provide the desired clinical outcomes due to inflammation-induced resistance amid inefficient drug delivery across the blood-brain barrier (BBB). The current study utilized solid lipid nanoparticles (SLNPs) for targeted delivery of [...] Read more.
Temozolomide (TMZ), the first-line chemotherapeutic drug against glioblastoma multiforme (GBM), often fails to provide the desired clinical outcomes due to inflammation-induced resistance amid inefficient drug delivery across the blood-brain barrier (BBB). The current study utilized solid lipid nanoparticles (SLNPs) for targeted delivery of TMZ against GBM. After successful formulation and characterization of SLNPs and conjugation with TMZ (SLNP-TMZ), their in-vitro anti-cancer efficacy and effect on the migratory potential of cancer cells were evaluated using temozolomide-sensitive (U87-S) as well as TMZ-resistant (U87-R) glioma cell lines. Elevated cytotoxicity and reduction in cell migration in both cell lines were observed with SLNP-TMZ as compared to the free drug (p < 0.05). Similar results were obtained in-vivo using an orthotopic xenograft mouse model (XM-S and XM-R), where a reduction in tumor size was observed with SLNP-TMZ treatment compared to TMZ. Concomitantly, higher concentrations of the drug were found in brain tissue resections of mice treated with SLNP-TMZ as compared to other vital organs than mice treated with free TMZ. Expression of inflammatory markers (Interleukin-1β, Interleukin-6 and Tumor Necrosis factor-α) in a resistant cell line (U87-R) and its respective mouse model (XM-R) were also found to be significantly elevated as compared to the sensitive U87-S cell line and its respective mouse model (XM-S). Thus, the in-vitro and in-vivo results of the study strongly support the potential application of SLNP-TMZ for TMZ-sensitive and resistant GBM therapy, indicatively through inflammatory mechanisms, and thus merit further detailed insights Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies for Glioblastoma)
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23 pages, 1330 KiB  
Article
Bioinformatics Strategies to Identify Shared Molecular Biomarkers That Link Ischemic Stroke and Moyamoya Disease with Glioblastoma
by Md Khairul Islam, Md Rakibul Islam, Md Habibur Rahman, Md Zahidul Islam, Md Al Amin, Kazi Rejvee Ahmed, Md Ataur Rahman, Mohammad Ali Moni and Bonglee Kim
Pharmaceutics 2022, 14(8), 1573; https://doi.org/10.3390/pharmaceutics14081573 - 28 Jul 2022
Cited by 1 | Viewed by 2918
Abstract
Expanding data suggest that glioblastoma is accountable for the growing prevalence of various forms of stroke formation, such as ischemic stroke and moyamoya disease. However, the underlying deterministic details are still unspecified. Bioinformatics approaches are designed to investigate the relationships between two pathogens [...] Read more.
Expanding data suggest that glioblastoma is accountable for the growing prevalence of various forms of stroke formation, such as ischemic stroke and moyamoya disease. However, the underlying deterministic details are still unspecified. Bioinformatics approaches are designed to investigate the relationships between two pathogens as well as fill this study void. Glioblastoma is a form of cancer that typically occurs in the brain or spinal cord and is highly destructive. A stroke occurs when a brain region starts to lose blood circulation and prevents functioning. Moyamoya disorder is a recurrent and recurring arterial disorder of the brain. To begin, adequate gene expression datasets on glioblastoma, ischemic stroke, and moyamoya disease were gathered from various repositories. Then, the association between glioblastoma, ischemic stroke, and moyamoya was established using the existing pipelines. The framework was developed as a generalized workflow to allow for the aggregation of transcriptomic gene expression across specific tissue; Gene Ontology (GO) and biological pathway, as well as the validation of such data, are carried out using enrichment studies such as protein–protein interaction and gold benchmark databases. The results contribute to a more profound knowledge of the disease mechanisms and unveil the projected correlations among the diseases. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies for Glioblastoma)
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