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Emerging Treatment of Glioblastoma Multiforme

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: 29 September 2024 | Viewed by 824

Special Issue Editor


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Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, 80131 Naples, Italy
Interests: molecular biology; brain tumor; oncology; circadian clock; nanotechnology

Special Issue Information

Dear Colleagues,

Glioblastoma multiforme (GBM) is one of the most aggressive tumors of the brain and, despite the continuous research developed over the last few decades, the prognosis for patients remains extremely poor. The current standard of care, the so-called Stupp protocol, includes surgery, radiotherapy, and chemotherapy, typically using the alkylating agent temozolomide (TMZ). The significant tumor heterogeneity of GBM promotes the selection of resistant subpopulations, leading to tumor recurrence and thus the universally lethal outcome. Moreover, the presence of a population of stem-like cells, the glioma stem cells (GSCs), characterized by the ability of self-renewal and tumorigenicity, contribute to therapy resistance, which remains a significant challenge to overcome. Furthermore, GBM creates a highly immunosuppressive environment with multiple mechanisms of immune evasion, preventing the effective functioning of various immunotherapy approaches. Indeed, phase III clinical studies with immune checkpoint inhibitors and vaccine therapy have been, thus far, disappointing. Remarkably, one crucial obstacle to effective treatment is the blood–brain barrier (BBB), which protects the CNS from environmental toxins, and the difficulty that some therapies have in passing the BBB. The drugs currently in use (chemotherapy drugs, immunotherapy or monoclonal antibodies) are all subject to perfusion differences in tumor vessels, resulting in different drug concentrations in various sites, which affects their clinical efficacy. Given that the currently approved treatments for GBM have largely been inadequate, new therapeutic strategies are urgently needed. This Special Issue aims to collect studies on existing and emerging therapies, including clinical trials, with a particular emphasis on the following topics:

  • Drug delivery technologies;
  • Cell delivery systems;
  • Radiosurgical techniques;
  • Adjuvants therapies;
  • Techniques to overcome the blood–brain barrier (BBB);
  • Gene therapy;
  • GSCs-targeting therapies;
  • Nanomedicine and nanotechnologies;
  • Potential GBM small-molecule inhibitors;
  • Immunotherapy (immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy).

Dr. Cristina Pagano
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 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • glioblastoma
  • emerging therapies
  • drug delivery
  • immunotherapy
  • nanomedicine
  • radiotherapy
  • viral therapy

Published Papers (1 paper)

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Research

18 pages, 3263 KiB  
Article
The MDM2–p53 Axis Represents a Therapeutic Vulnerability Unique to Glioma Stem Cells
by Yurika Nakagawa-Saito, Yuta Mitobe, Keita Togashi, Shuhei Suzuki, Asuka Sugai, Senri Takenouchi, Kazuki Nakamura, Yukihiko Sonoda, Chifumi Kitanaka and Masashi Okada
Int. J. Mol. Sci. 2024, 25(7), 3948; https://doi.org/10.3390/ijms25073948 - 02 Apr 2024
Viewed by 593
Abstract
The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests [...] Read more.
The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways. The results obtained showed that MDM2 expression was substantially higher in glioma stem cells than in their non-stem cell counterparts and also that the inhibition of MDM2, either genetically or pharmacologically, induced a more pronounced activation of the p53 pathway and apoptotic cell death in the former than in the latter. Specifically, the inhibition of MDM2 caused a p53-dependent increase in the expression of BAX and PUMA and a decrease in the expression of survivin, both of which significantly contributed to the apoptotic death of glioma stem cells. The present study identified the MDM2–p53 axis as a novel therapeutic vulnerability, or an Achilles’ heel, which is unique to glioma stem cells. Our results, which suggest that non-stem, bulk tumor cells are less sensitive to MDM2 inhibitors, may help guide the selection of glioblastoma patients suitable for MDM2 inhibitor therapy. Full article
(This article belongs to the Special Issue Emerging Treatment of Glioblastoma Multiforme)
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