International Journal of Molecular Sciences

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Dr. José Ángel Campos Sandoval

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1. Departamento de Biología Molecular y Bioquímica, Canceromics Lab, Universidad de Málaga, 29071 Málaga, Spain
2. Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Málaga, Spain
Interests: cancer omics; cancer metabolic reprogramming; tumor nitrogen metabolism; structure-function studies; drug design
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Dear Colleagues,

Glioblastoma is one of the most feared types of cancer. Although it affects only a minor percentage of the human population, patients with glioblastoma show a very bad prognosis, with a median overall survival rate of only 12–16 months and a 5-year survival rate of 5%, so novel treatment strategies are urgently needed. The current standard of care (known as the Stupp protocol), consisting of maximal surgical resection followed by radiotherapy with concomitant and maintenance chemotherapy with the alkylating agent temozolomide, has not changed since its publication in 2005 and is only palliative: unfortunately, after a temporary remission, almost all patients will experience tumor recurrence due to the impossibility to eliminate all tumor cells, with fatal consequences. Despite the significant research effort in the last two decades dedicated to unraveling the genetics and molecular biology of glioblastomas, this has not translated into an improvement in the survival of patients with this tumor. So far, several targeted therapies (such as the anti-angiogenic antibody bevacizumab) have shown minimal benefit when tested in clinical trials. The inefficiency of these treatments is due to several factors, mainly the existence of a population of radio-chemoresistant cells called glioblastoma stem cells. These cells possess self-renewal and proliferative capacities, which allow them to escape the standard therapy giving rise to a tumor mass more aggressive than the primary tumor. Likewise, the blood-brain and blood-tumor barriers and the immune components of the tumor microenvironment are also highly relevant in this resistance.

This Special Issue, entitled Emerging Therapies for Glioblastoma, will offer an overview of the novel approaches currently being developed that will hopefully elicit tangible benefits for glioblastoma patients. These strategies include, among others: the use of oncolytic viruses, dendritic and chimeric antigen receptor T cells, and immune checkpoint inhibitors to trigger anti-tumor immune responses; spherical nucleic acids nanoconjugates to overcome the blood-brain and brain-tumor barriers, and precisely deliver therapeutic molecules; drug repurposing to identify new drug candidates, etc. This issue will mainly contain experimental papers, but up-to-date reviews are welcome.

Dr. José Ángel Campos Sandoval
Guest Editor

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Keywords

glioblastoma
drug repurposing
drug delivery
biomaterials
immunotherapy
immune checkpoint inhibitors
oncolytic virotherapy
CAR-T cells
dendritic cell vaccination
spherical nucleic acids
gene therapy

Published Papers (2 papers)

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Research

12 pages, 1772 KiB

Open AccessArticle

Differential H₂O₂ Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation

by Amira Zaher, Kranti A. Mapuskar, Jann N. Sarkaria, Douglas R. Spitz, Michael S. Petronek and Bryan G. Allen

Int. J. Mol. Sci. 2023, 24(24), 17158; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417158 - 05 Dec 2023

Viewed by 824

Abstract

Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH⁻) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH⁻. P-AscH⁻ (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH⁻ (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H₂O₂ metabolism that potentially drives differential P-AscH⁻ toxicity. Taken together, these data suggest that P-AscH⁻ may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC. Full article

(This article belongs to the Special Issue Emerging Therapies for Glioblastoma)

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22 pages, 2742 KiB

Open AccessArticle

Deciphering the Action of Neuraminidase in Glioblastoma Models

by Nathalie Baeza-Kallee, Raphaël Bergès, Victoria Hein, Stéphanie Cabaret, Jeremy Garcia, Abigaëlle Gros, Emeline Tabouret, Aurélie Tchoghandjian, Carole Colin and Dominique Figarella-Branger

Int. J. Mol. Sci. 2023, 24(14), 11645; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411645 - 19 Jul 2023

Cited by 4 | Viewed by 1981

Abstract

Glioblastoma (GBM) contains cancer stem cells (CSC) that are resistant to treatment. GBM CSC expresses glycolipids recognized by the A2B5 antibody. A2B5, induced by the enzyme ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl transferase 3 (ST8Sia3), plays a crucial role in the proliferation, migration, clonogenicity and tumorigenesis of GBM CSC. Our aim was to characterize the resulting effects of neuraminidase that removes A2B5 in order to target GBM CSC. To this end, we set up a GBM organotypic slice model; quantified A2B5 expression by flow cytometry in U87-MG, U87-ST8Sia3 and GBM CSC lines, treated or not by neuraminidase; performed RNAseq and DNA methylation profiling; and analyzed the ganglioside expression by liquid chromatography–mass spectrometry in these cell lines, treated or not with neuraminidase. Results demonstrated that neuraminidase decreased A2B5 expression, tumor size and regrowth after surgical removal in the organotypic slice model but did not induce a distinct transcriptomic or epigenetic signature in GBM CSC lines. RNAseq analysis revealed that OLIG2, CHI3L1, TIMP3, TNFAIP2, and TNFAIP6 transcripts were significantly overexpressed in U87-ST8Sia3 compared to U87-MG. RT-qPCR confirmed these results and demonstrated that neuraminidase decreased gene expression in GBM CSC lines. Moreover, neuraminidase drastically reduced ganglioside expression in GBM CSC lines. Neuraminidase, by its pleiotropic action, is an attractive local treatment against GBM. Full article

(This article belongs to the Special Issue Emerging Therapies for Glioblastoma)

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