Special Issue "Identification of Molecular Targets and Anti-cancer Agents in Glioblastoma Multiforme: New Perspectives for Cancer Therapy"

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (5 February 2023) | Viewed by 2409

Special Issue Editors

Department of Drug and Health Sciences, University of Catania, 95100 Catania, Italy
Interests: neuroanatomy; neuroscience; neuropeptides; neural stem cells; identification of carcinogenic bi-omarkers; study of molecular mechanisms involved in cancers progression
Special Issues, Collections and Topics in MDPI journals
Department of Biomedicine, Neurosciences and Advanced Diagnostic (BiND), Human Anatomy Section, University of Palermo, 90127 Palermo, Italy
Interests: extracellular vesicles; exosomes; miRNA; liquid biopsy; cancerogenesis; anatomy; molecular chaperones; heat shock proteins; extracellular chaperones
Special Issues, Collections and Topics in MDPI journals
Laboratory of Neuronal Networks, Department of Mental and Physical Health and Preventive Medicine, University of Campania ''Luigi Vanvitelli", 80138 Naples, Italy
Interests: central nervous system plasticity; glioblastoma microenvironment; tumor–glia inter-action; blood–brain barrier; peripheral nerve injury

Special Issue Information

Dear Colleagues,

Glioblastoma multiforme (GBM) or grade IV astrocytoma is the deadliest form of brain tumor. To date, the standard therapy consists of a multimodal approach combining surgery, radiation and chemotherapy with temozolomide. However, tumor relapse frequently occurs, and survival rates are poor in patients. GBM’s poor prognosis is also attributable to therapeutic resistance to standard therapy. The therapeutic resistance is mainly due to the presence of glioblastoma stem cells (GSCs) inside the tumor core, and could be dependent on innate differences in clonogenic GSCs’ sensitivity to conventional therapy. GSCs and mature cells reside in specific regions of the cancer mass forming tumor niches, including hypoxic, vascular and perivascular niches that support GSCs’ quiescent status and contribute to create a microenvironmental cue sustaining their pluripotent potential which determines cancer aggressiveness and therapy resistance. The resident cells of the central nervous system and blood-derived elements are recruited into the niches for a functional symbiosis that ensures energy sources, invasiveness, immune escape, and drug resistance to the GBM, allowing its progression.

Furthermore, GBM is characterized by intratumor and inter-patient molecular heterogeneity that may underlie differences in patient sensitivity to therapy and prognosis.

Although the research in this field is rapidly evolving, there is a persistent variability of treatment effectiveness and difficulty in performing early diagnosis. The identification of non-invasive alternatives to standard diagnostic approaches, such as liquid biopsy, as well as novel treatment strategies and effective therapeutic targets, could offer new directions for future therapeutic management.

This Special Issue considers original research articles, review articles, and commentaries on the following themes: i) identification of new molecular targeted and/or prognostic biomarkers for GBM; ii) recent advances in combined therapy to existing gold-standard treatment; iii) ongoing clinical trials in the treatment of GBM.

Prof. Dr. Agata Grazia D'Amico
Prof. Dr. Celeste Caruso Bavisotto
Dr. Assunta Virtuoso
Guest Editors

Manuscript Submission Information

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Keywords

  • glioblastoma multiforme
  • tumor microenvironment
  • hypoxic niches
  • vascular niches
  • liquid biopsy
  • extracellular vesicles
  • immunotherapy
  • glial cells
  • neurons
  • macrophages

Published Papers (3 papers)

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Research

Communication
Technical Pearls to Effectively Use 5-ALA in Fluorescence-Guided Tumor Resection—5 Lessons from the Operating Room
Brain Sci. 2023, 13(3), 411; https://doi.org/10.3390/brainsci13030411 - 27 Feb 2023
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Abstract
Background: Since its introduction in 2007 in Europe and in 2017 in the United States, 5-ALA has demonstrated an undisputed advantage in providing real-time tumor visualization. The aim of the present paper is to summarize our institutional experience over a decade of routine [...] Read more.
Background: Since its introduction in 2007 in Europe and in 2017 in the United States, 5-ALA has demonstrated an undisputed advantage in providing real-time tumor visualization. The aim of the present paper is to summarize our institutional experience over a decade of routine 5-ALA-guided procedures in order to provide five surgical tricks to ease surgical workflow. Methods: Data were collected from 822 patients diagnosed with histopathologically confirmed high-grade gliomas (HGG)—according to the WHO 2021 criteria—who underwent surgery at the Fondazione Policlinico Universitario Agostino Gemelli between January 2012 and January 2022. Results: From our large institutional experience, the learned technical pearls were grouped in five distinct domains: 1. Analysis of visualization, overall workflow, and technical recommendations to improve intraoperative set-up; 2. Techniques to reduce the risk of inadvertent residuals and failure to evocate fluorescence; 3. Analysis of specific surgical conditions favoring remnants; 4. Assessment of different degrees of fluorescence and their surgical meaning; 5. Analysis of false positive cases. Conclusions: With all the limitations of a qualitative and retrospective analysis, this paper was specifically conceived as a vademecum for educational purposes to promote and maximize 5-ALA employment. Full article
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Communication
Identification of Dysregulated microRNAs in Glioblastoma Stem-like Cells
Brain Sci. 2023, 13(2), 350; https://doi.org/10.3390/brainsci13020350 - 18 Feb 2023
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Abstract
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite multimodal therapy, median survival is poor at 12–15 months. At the molecular level, radio-/chemoresistance and resulting tumor progression are attributed to a small fraction of tumor cells, termed glioblastoma [...] Read more.
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite multimodal therapy, median survival is poor at 12–15 months. At the molecular level, radio-/chemoresistance and resulting tumor progression are attributed to a small fraction of tumor cells, termed glioblastoma stem-like cells (GSCs). These CD133-expressing, self-renewing cells display the properties of multi-lineage differentiation, resulting in the heterogenous composition of GBM. MicroRNAs (miRNAs) as regulators of gene expression at the post-transcriptional level can alter many pathways pivotal to cancer stem cell fate. This study explored changes in the miRNA expression profiles in patient-derived GSCs altered on differentiation into glial fiber acid protein (GFAP)-expressing, astrocytic tumor cells using a polymerase chain reaction (PCR) array. Initially, 22 miRNAs showed higher expression in GSCs and 9 miRNAs in differentiated cells. The two most downregulated miRNAs in differentiated GSCs were miR-17-5p and miR-425-5p, whilst the most upregulated miRNAs were miR-223-3p and let-7-5p. Among those, miR-425-5p showed the highest consistency in an upregulation in all three GSCs. By transfection of a 425-5p miRNA mimic, we demonstrated downregulation of the GFAP protein in differentiated patient-derived GBM cells, providing potential evidence for direct regulation of miRNAs in the GSC/GBM cell transition. Full article
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Article
Single-Cell Sequencing Analysis Identified ASTN2 as a Migration Biomarker in Adult Glioblastoma
Brain Sci. 2022, 12(11), 1472; https://doi.org/10.3390/brainsci12111472 - 30 Oct 2022
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Abstract
Glioblastoma is the most common and aggressive primary central nervous system malignant tumors. With the development of targeted sequencing and proteomic profiling technology, some new tumor types have been established and a series of novel molecular markers have also been identified. The 2021 [...] Read more.
Glioblastoma is the most common and aggressive primary central nervous system malignant tumors. With the development of targeted sequencing and proteomic profiling technology, some new tumor types have been established and a series of novel molecular markers have also been identified. The 2021 updated World Health Organization classification of central nervous system tumors first mentioned the classification of adult glioma and pediatric glioma based on the molecular diagnosis. Thus, we used single-cell RNA sequencing analysis to explore the diversity and similarities in the occurrence and development of adult and pediatric types. ASTN2, which primarily encodes astrotactin, has been reported to be dysregulated in various neurodevelopmental disorders. Although some studies have demonstrated that ASTN2 plays an important role in glial-guided neuronal migration, there are no studies about its impact on glioblastoma cell migration. Subsequent single-cell RNA sequencing revealed ASTN2 to be a hub gene of a cell cluster which had a poor effect on clinical prognosis. Eventually, a western blot assay and a wound-healing assay first confirmed that ASTN2 expression in glioblastoma cell lines is higher than that in normal human astrocytes and affects the migration ability of glioblastoma cells, making it a potential therapeutic target. Full article
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