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Novel Therapeutic Treatments to Target Glioblastoma Intratumoral Heterogeneity and Plasticity 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 4545

Special Issue Editor

Centre for Cancer Biology, SA Pathology and the University of South of Australia, Adelaide, SA 5000, Australia
Interests: brain tumors; precision oncology; patient-derived organoids; transcriptomics; proteomics; deep learning; microscopy; brain disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a five-year relative survival (4.6% only at 5 years) that has remained stable over the last three decades. Intratumour heterogeneity is a key feature that makes GBM one of the most deadly types of tumours, which results from the capacity of GBM-cancer stem cells to interconvert between different cancer cell populations in response to changes in the tumour microenvironment and/or different drug treatments. This not only explains the poor performance in single drug therapy in GBM but also reveals a key role for GBM plasticity, the interaction of GBM and the microenvironment and brain cancer progression, and thus constitutes a novel paradigm that needs to be addressed in order to find better treatments for patients with GBM.

As Volume 1 of the Special Issue “Novel Therapeutic Treatments to Target Glioblastoma Intratumoral Heterogeneity and Plasticity” was successful, we reopen this issue again in the International Journal of Molecular Sciences (https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms, ISSN 1422-0067, IF 5.924, JCR Category Q1). This second Special Issue will be dedicated to publishing original work and reviews in the areas of neuro-oncology, pharmacology, bioinformatics, cell and cancer biology, drug screenings, bioengineering, genetics, and others, on aspects that will contribute to better understanding at the molecular level of the functional role of heterogeneity and plasticity in glioblastoma biology and treatment.

https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/glioblastoma_novel

Dr. Guillermo Gomez
Guest Editor

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Keywords

  • glioblastoma
  • heterogeneity
  • microenvironment
  • stemness
  • cancer stem cells
  • immune system
  • cancer cell resistance
  • perivascular niche
  • necrosis
  • therapy

Published Papers (2 papers)

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Research

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22 pages, 4975 KiB  
Article
Polysialic Acid Sustains the Hypoxia-Induced Migration and Undifferentiated State of Human Glioblastoma Cells
by Paolo Rosa, Sofia Scibetta, Giuseppe Pepe, Giorgio Mangino, Luca Capocci, Sam J. Moons, Thomas J. Boltje, Francesco Fazi, Vincenzo Petrozza, Alba Di Pardo, Vittorio Maglione and Antonella Calogero
Int. J. Mol. Sci. 2022, 23(17), 9563; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179563 - 24 Aug 2022
Cited by 7 | Viewed by 1834
Abstract
Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, [...] Read more.
Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of α2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM. Full article
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Review

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19 pages, 823 KiB  
Review
Exosomes as Novel Diagnostic Biomarkers and Therapeutic Tools in Gliomas
by Panagiotis Skouras, Antonios N. Gargalionis and Christina Piperi
Int. J. Mol. Sci. 2023, 24(12), 10162; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241210162 - 15 Jun 2023
Cited by 3 | Viewed by 2278
Abstract
Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of transmitting signals between cells and coordinating cellular communication. By this means, they are ultimately involved in physiology and disease, including development, homeostasis, [...] Read more.
Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of transmitting signals between cells and coordinating cellular communication. By this means, they are ultimately involved in physiology and disease, including development, homeostasis, and immune system regulation, as well as contributing to tumor progression and neurodegenerative diseases pathology. Recent studies have shown that gliomas secrete a panel of exosomes which have been associated with cell invasion and migration, tumor immune tolerance, potential for malignant transformation, neovascularization, and resistance to treatment. Exosomes have therefore emerged as intercellular communicators, which mediate the tumor–microenvironment interactions and exosome-regulated glioma cell stemness and angiogenesis. They may induce tumor proliferation and malignancy in normal cells by carrying pro-migratory modulators from cancer cells as well as many different molecular cancer modifiers, such as oncogenic transcripts, miRNAs, mutant oncoproteins, etc., which promote the communication of cancer cells with the surrounding stromal cells and provide valuable information on the molecular profile of the existing tumor. Moreover, engineered exosomes can provide an alternative system for drug delivery and enable efficient treatment. In the present review, we discuss the latest findings regarding the role of exosomes in glioma pathogenesis, their utility in non-invasive diagnosis, and potential applications to treatment. Full article
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