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Cells
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Therapeutic Targets in Glioblastoma
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Therapeutic Targets in Glioblastoma

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 20 October 2025 | Viewed by 4402

Special Issue Editors

Dr. Candice Mazewski

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Genetics, Midwestern University, 555 31st St., Downers Grove, IL 60515, USA
Interests: glioblastoma; colorectal cancer; solid tumors; signaling targets; complementary medicine; nutrient-sensing; nutrition; plants; polyphenols; bioactives; microbiome; gut–brain axis
Dr. Frank Eckerdt

E-Mail Website
Guest Editor
1. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA
2. Division of Hematology-Oncology, Department of Medicine, Northwestern University, Chicago, IL 60611, USA
Interests: cancer biology; cell signaling; signal transduction; cancer stem cells; neuro-oncology; cell biology; cell division; clinical research; drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma (grade 4 brain cancer) is among the most difficult cancers to treat due in part to its high tumor heterogeneity and the protective blood–brain barrier limiting tumor penetration by therapeutics. Despite ongoing efforts, enhanced therapeutic targeting in glioblastoma has remained elusive, and a dismal 5-year survival rate persists. Expanding our understanding of the signaling changes in glioblastoma cells and the highly plastic glioma stem cell population is critical for developing more effective treatment options. Analyzing alternative targets and approaches is necessary to develop innovative therapeutic options that improve overall survival for glioblastoma patients.

For this Special Issue, we invite submissions in the form of original research articles and reviews that explore signaling dynamics and therapeutic strategies in glioblastoma. Topics may include signaling alterations linked to glioblastoma initiation, progression, and resistance and those affecting glioma stem cell populations. We also encourage submissions that explore alternative therapeutic approaches, including investigations of cell metabolism, nutrient-sensing pathways, and the impact of dietary components on signaling.

Dr. Candice Mazewski
Dr. Frank Eckerdt
Guest Editors

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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioblastoma
  • signaling targets
  • blood-brain-barrier
  • complementary and alternative medicine
  • combination therapy
  • glioma stem cells
  • progression
  • resistance
  • nutrient-sensing

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Published Papers (4 papers)

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Research

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26 pages, 18146 KiB  
Article
Trying to Kill a Killer; Impressive Killing of Patient Derived Glioblastoma Cultures Using NK-92 Natural Killer Cells Reveals Both Sensitive and Highly Resistant Glioblastoma Cells
by Jane Yu, Hyeon Joo Kim, Jordyn Reinecke, James Hucklesby, Tennille Read, Akshata Anchan, Catherine E. Angel and Euan Scott Graham
Cells 2025, 14(1), 53; https://doi.org/10.3390/cells14010053 - 5 Jan 2025
Viewed by 1010
Abstract
The overall goal of this work was to assess the ability of Natural Killer cells to kill cultures of patient-derived glioblastoma cells. Herein we report impressive levels of NK-92 mediated killing of various patient-derived glioblastoma cultures observed at ET (effector: target) ratios of [...] Read more.
The overall goal of this work was to assess the ability of Natural Killer cells to kill cultures of patient-derived glioblastoma cells. Herein we report impressive levels of NK-92 mediated killing of various patient-derived glioblastoma cultures observed at ET (effector: target) ratios of 5:1 and 1:1. This enabled direct comparison of the degree of glioblastoma cell loss across a broader range of glioblastoma cultures. Importantly, even at high ET ratios of 5:1, there are always subpopulations of glioblastoma cells that prove very challenging to kill that evade the NK-92 cells. Of value in this study has been the application of ECIS (Electric Cell–Substrate Impedance Sensing) biosensor technology to monitor the glioblastoma cells in real-time, enabling temporal assessment of the NK-92 cells. ECIS has been powerful in revealing that at higher ET ratios, the glioblastoma cells are acutely sensitive to the NK-92 cells, and the observed glioblastoma cell death is supported by the high-content imaging data. Moreover, long-term ECIS experiments reveal that the surviving glioblastoma cells were then able to grow and reseed the culture, which was evident 300–500 h after the addition of the NK-92 cells. This was observed for multiple glioblastoma lines. In addition, our imaging provides evidence that some NK-92 cells appear to be compromised early, which would be consistent with potent evasive mechanisms by the glioblastoma tumour cells. This research strongly highlights the potential for NK-92 cells to kill glioblastoma tumour cells and provides a basis to identify the mechanism utilised by the surviving glioblastoma cells that we now need to target to achieve maximal cytolysis of the resistant glioblastoma cells. It is survival of the highly resistant glioblastoma clones that results in tumour relapse. Full article
(This article belongs to the Special Issue Therapeutic Targets in Glioblastoma)
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Review

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26 pages, 1695 KiB  
Review
Therapeutic Targets in Glioblastoma: Molecular Pathways, Emerging Strategies, and Future Directions
by Justin Tang, Nishika Karbhari and Jian L. Campian
Cells 2025, 14(7), 494; https://doi.org/10.3390/cells14070494 - 26 Mar 2025
Cited by 1 | Viewed by 975
Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid growth, invasive infiltration into surrounding brain tissue, and resistance to conventional therapies. Despite advancements in surgery, radiotherapy, and chemotherapy, median survival remains approximately 15 months, underscoring the urgent need [...] Read more.
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid growth, invasive infiltration into surrounding brain tissue, and resistance to conventional therapies. Despite advancements in surgery, radiotherapy, and chemotherapy, median survival remains approximately 15 months, underscoring the urgent need for innovative treatments. Key considerations informing treatment development include oncogenic genetic and epigenetic alterations that may dually serve as therapeutic targets and facilitate treatment resistance. Various immunotherapeutic strategies have been explored and continue to be refined for their anti-tumor potential. Technical aspects of drug delivery and blood–brain barrier (BBB) penetration have been addressed through novel vehicles and techniques including the incorporation of nanotechnology. Molecular profiling has emerged as an important tool to individualize treatment where applicable, and to identify patient populations with the most drug sensitivity. The goal of this review is to describe the spectrum of potential GBM therapeutic targets, and to provide an overview of key trial outcomes. Altogether, the progress of clinical and preclinical work must be critically evaluated in order to develop therapies for GBM with the strongest therapeutic efficacy. Full article
(This article belongs to the Special Issue Therapeutic Targets in Glioblastoma)
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30 pages, 1360 KiB  
Review
Angiogenesis in Glioblastoma—Treatment Approaches
by Agnieszka Nowacka, Maciej Śniegocki, Wojciech Smuczyński, Dominika Bożiłow and Ewa Ziółkowska
Cells 2025, 14(6), 407; https://doi.org/10.3390/cells14060407 - 11 Mar 2025
Viewed by 906
Abstract
Glioblastoma, the most common primary malignant brain tumor in adults, carries a poor prognosis, with a median survival of just 15 months, significantly impacting patients’ quality of life. The aggressive growth of these highly vascularized tumors relies heavily on angiogenesis, driven primarily by [...] Read more.
Glioblastoma, the most common primary malignant brain tumor in adults, carries a poor prognosis, with a median survival of just 15 months, significantly impacting patients’ quality of life. The aggressive growth of these highly vascularized tumors relies heavily on angiogenesis, driven primarily by vascular endothelial growth factor-A. Therefore, VEGF signaling pathway has become a prime therapeutic target in GBM treatment over the past decade. While anti-angiogenic treatment showed promise, agents like bevacizumab have ultimately failed to improve overall survival. This highlights the presence of compensatory angiogenic mechanisms that bypass VEGF inhibition, necessitating further investigation into resistance mechanisms and the development of more effective therapeutic strategies. This review examined the current landscape of anti-angiogenic agents for GBM, analyzed the mechanisms driving resistance to these therapies, and explored potential strategies for enhancing their effectiveness. Full article
(This article belongs to the Special Issue Therapeutic Targets in Glioblastoma)
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25 pages, 3398 KiB  
Review
Harnessing Arsenic Derivatives and Natural Agents for Enhanced Glioblastoma Therapy
by Bo Yuan and Hidetomo Kikuchi
Cells 2024, 13(24), 2138; https://doi.org/10.3390/cells13242138 - 23 Dec 2024
Viewed by 1036
Abstract
Glioblastoma (GBM) is the most common and lethal intracranial tumor in adults. Despite advances in the understanding of the molecular events responsible for disease development and progression, survival rates and mortality statistics for GBM patients have been virtually unchanged for decades and chemotherapeutic [...] Read more.
Glioblastoma (GBM) is the most common and lethal intracranial tumor in adults. Despite advances in the understanding of the molecular events responsible for disease development and progression, survival rates and mortality statistics for GBM patients have been virtually unchanged for decades and chemotherapeutic drugs used to treat GBM are limited. Arsenic derivatives, known as highly effective anticancer agents for leukemia therapy, has been demonstrated to exhibit cytocidal effects toward GBM cells by inducing cell death, cell cycle arrest, inhibition of migration/invasion, and angiogenesis. Differentiation induction of glioma stem-like cells (GSCs) and inhibition of neurosphere formation have also been attributed to the cytotoxicity of arsenic derivatives. Intriguingly, similar cytotoxic effects against GBM cells and GSCs have also been observed in natural agents such as anthocyanidins, tetrandrine, and bufadienolides. In the current review, we highlight the available data on the molecular mechanisms underlying the multifaceted anticancer activity of arsenic compounds and natural agents against cancer cells, especially focusing on GBM cells and GCSs. We also outline possible strategies for developing anticancer therapy by combining natural agents and arsenic compounds, as well as temozolomide, an alkylating agent used to treat GBM, in terms of improvement of chemotherapy sensitivity and minimization of side effects. Full article
(This article belongs to the Special Issue Therapeutic Targets in Glioblastoma)
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