Gliomas: Signaling Pathways, Molecular Mechanisms and Novel Therapies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 2703

Special Issue Editor

Special Issue Information

Dear Colleagues,

This Special Issue delves into the rapidly evolving field of glioma's molecular intricacies, with a specific focus on the role of signal pathways and their implications for novel therapeutic strategies. Gliomas, originating from the transformation of glial cells, are marked by a complex array of genetic, epigenetic, and signaling alterations. These include mutations in pivotal genes such as IDH1/2, TP53, and ATRX in lower-grade gliomas; PTEN, EGFR, and PDGFRA in primary glioblastomas; and DNA methylation and histone modifications. Crucially, this Special Issue highlights how disruptions in signal transduction pathways, such as the RTK/RAS/PI(3)K pathway, play a central role in glioma pathogenesis and offer potential targets for therapy.

A key focus of this Special Issue is on the innovative treatment strategies emerging in response to these challenges, particularly those targeting aberrant signaling in gliomas. Advances in immunotherapy, such as checkpoint inhibitors and CAR T-cell therapy, are being adapted to target the immunosuppressive tumor microenvironment and navigate the blood–brain barrier (BBB). Additionally, we explore gene therapy techniques using viral vectors for direct tumor targeting and the application of nanomedicine for enhanced drug delivery, both of which are critical in manipulating signaling pathways within the tumor.

The objective is to present a comprehensive overview of the current state of glioma treatment research, with a special emphasis on signal pathways. This includes illustrating the promising therapeutic avenues that are arising and acknowledging the considerable challenges that remain. We aim to foster a deeper understanding of these advancements and hurdles among researchers, clinicians, and stakeholders, with the ultimate goal of driving forward innovations that promise improved outcomes for glioma patients.

Dr. Hung-Pei Tsai
Guest Editor

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Keywords

  • glioma
  • molecular pathology
  • blood–brain barrier
  • immunotherapy
  • microenvironment
  • nanomedicine

Published Papers (4 papers)

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Research

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15 pages, 3859 KiB  
Article
High PGC-1α Expression as a Poor Prognostic Indicator in Intracranial Glioma
by Yu-Wen Cheng, Jia-Hau Lee, Chih-Hui Chang, Tzu-Ting Tseng, Chee-Yin Chai, Ann-Shung Lieu and Aij-Lie Kwan
Biomedicines 2024, 12(5), 979; https://doi.org/10.3390/biomedicines12050979 - 29 Apr 2024
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Abstract
Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial [...] Read more.
Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes. Full article
(This article belongs to the Special Issue Gliomas: Signaling Pathways, Molecular Mechanisms and Novel Therapies)
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13 pages, 5942 KiB  
Article
Antitumor Efficacy of Arylquin 1 through Dose-Dependent Cytotoxicity, Apoptosis Induction, and Synergy with Radiotherapy in Glioblastoma Models
by Ann-Shung Lieu, Yu-Chi Pan, Jia-Hau Lee, Yuan-Chin Hsieh, Chien-Ju Lin, Ya-Ling Hsu, Kung-Chao Chang, Shih-Hsun Kuo, Tzu-Ting Tseng and Hung-Pei Tsai
Biomedicines 2024, 12(4), 907; https://doi.org/10.3390/biomedicines12040907 - 19 Apr 2024
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Abstract
Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by rapid growth and resistance to conventional therapies. Current treatments offer limited effectiveness, leading to poor survival rates and the need for novel therapeutic strategies. Arylquin 1 has emerged as a potential [...] Read more.
Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by rapid growth and resistance to conventional therapies. Current treatments offer limited effectiveness, leading to poor survival rates and the need for novel therapeutic strategies. Arylquin 1 has emerged as a potential therapeutic candidate because of its unique mechanism of inducing apoptosis in cancer cells without affecting normal cells. This study investigated the efficacy of Arylquin 1 against GBM using the GBM8401 and A172 cells by assessing its dose-dependent cytotoxicity, apoptosis induction, and synergy with radiotherapy. In vitro assays demonstrated a significant reduction in cell viability and increased apoptosis, particularly at high concentrations of Arylquin 1. Migration and invasion analyses revealed notable inhibition of cellular motility. In vivo experiments on NU/NU nude mice with intracranially implanted GBM cells revealed that Arylquin 1 substantially reduced tumor growth, an effect magnified by concurrent radiotherapy. These findings indicate that by promoting apoptosis and enhancing radiosensitivity, Arylquin 1 is a potent therapeutic option for GBM treatment. Full article
(This article belongs to the Special Issue Gliomas: Signaling Pathways, Molecular Mechanisms and Novel Therapies)
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21 pages, 12760 KiB  
Article
Significant Genes Associated with Mortality and Disease Progression in Grade II and III Glioma
by Bo Mi Choi, Jin Hwan Cheong, Je Il Ryu, Yu Deok Won, Kyueng-Whan Min and Myung-Hoon Han
Biomedicines 2024, 12(4), 858; https://doi.org/10.3390/biomedicines12040858 - 12 Apr 2024
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Abstract
Background: The Wnt/β-catenin pathway plays a critical role in the tumorigenesis and maintenance of glioma stem cells. This study aimed to evaluate significant genes associated with the Wnt/β-catenin pathway involved in mortality and disease progression in patients with grade II and III glioma, [...] Read more.
Background: The Wnt/β-catenin pathway plays a critical role in the tumorigenesis and maintenance of glioma stem cells. This study aimed to evaluate significant genes associated with the Wnt/β-catenin pathway involved in mortality and disease progression in patients with grade II and III glioma, using the Cancer Genome Atlas (TCGA) database. Methods: We obtained clinicopathological information and mRNA expression data from 515 patients with grade II and III gliomas from the TCGA database. We performed a multivariate Cox regression analysis to identify genes independently associated with glioma prognosis. Results: The analysis of 34 genes involved in Wnt/β-catenin signaling demonstrated that four genes (CER1, FRAT1, FSTL1, and RPSA) related to the Wnt/β-catenin pathway were significantly associated with mortality and disease progression in patients with grade II and III glioma. We also identified additional genes related to the four significant genes of the Wnt/β-catenin pathway mentioned above. The higher expression of BMP2, RPL18A, RPL19, and RPS12 is associated with better outcomes in patients with glioma. Conclusions: Using a large-scale open database, we identified significant genes related to the Wnt/β-catenin signaling pathway associated with mortality and disease progression in patients with grade II and III gliomas. Full article
(This article belongs to the Special Issue Gliomas: Signaling Pathways, Molecular Mechanisms and Novel Therapies)
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Review

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15 pages, 1447 KiB  
Review
Microbubble-Enhanced Focused Ultrasound for Infiltrating Gliomas
by Alexandra A. Seas, Adarsha P. Malla, Nima Sharifai, Jeffrey A. Winkles, Graeme F. Woodworth and Pavlos Anastasiadis
Biomedicines 2024, 12(6), 1230; https://doi.org/10.3390/biomedicines12061230 - 1 Jun 2024
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Abstract
Infiltrating gliomas are challenging to treat, as the blood-brain barrier significantly impedes the success of therapeutic interventions. While some clinical trials for high-grade gliomas have shown promise, patient outcomes remain poor. Microbubble-enhanced focused ultrasound (MB-FUS) is a rapidly evolving technology with demonstrated safety [...] Read more.
Infiltrating gliomas are challenging to treat, as the blood-brain barrier significantly impedes the success of therapeutic interventions. While some clinical trials for high-grade gliomas have shown promise, patient outcomes remain poor. Microbubble-enhanced focused ultrasound (MB-FUS) is a rapidly evolving technology with demonstrated safety and efficacy in opening the blood-brain barrier across various disease models, including infiltrating gliomas. Initially recognized for its role in augmenting drug delivery, the potential of MB-FUS to augment liquid biopsy and immunotherapy is gaining research momentum. In this review, we will highlight recent advancements in preclinical and clinical studies that utilize focused ultrasound to treat gliomas and discuss the potential future uses of image-guided precision therapy using focused ultrasound. Full article
(This article belongs to the Special Issue Gliomas: Signaling Pathways, Molecular Mechanisms and Novel Therapies)
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