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Pharmaceuticals
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Drug Therapy for Glioma
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Drug Therapy for Glioma

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (25 May 2024) | Viewed by 6377

Special Issue Editors

Dr. Kok Siong Chen

E-Mail Website
Guest Editor
Center for Stem Cell and Translational Immunotherapy, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Interests: glioblastoma; neuro-oncology; cancer vaccines; cancer immunotherapy; tumor initiation and progression
Dr. Lucia Moreno-Lama

E-Mail Website
Guest Editor
Center for Stem Cell and Translational Immunotherapy, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Interests: immuno-oncology; biomedicine; immunotherapy; genetic engineering; cell therapy; immune checkpoint; nanobodies; cytokines; oncolytic viruses; HDACi
Dr. Filippo Rossignoli

E-Mail Website
Guest Editor
Center for Stem Cell and Translational Immunotherapy, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Interests: gene therapy; cancer, immune therapy; adoptive cell therapy; immunology

Special Issue Information

Dear Colleagues,

Gliomas are the most common brain tumors originating from glial cells. Among the malignant gliomas, grade IV glioma, or glioblastoma (GBM), is the most aggressive form. Despite advances in surgery, radiotherapy and chemotherapy, the median survival of GBM patients remains at just 12–15 months. Adjuvant chemotherapy is an important treatment component, yet standard systemic routes often demonstrate toxicity and limited crossing through the blood–brain-barrier. Due to the significant inter-tumoral molecular heterogeneity of GBMs, biomarker-driven therapy that targets specific alterations in GBM is increasingly recognized as the optimum method to improve patient outcomes and reduce toxicity. Therefore, more pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective treatment options.

This Special Issue aims to review the potential novel drug agents, and the current status of preclinical and clinical trials, and explore the challenges and future perspectives in glioma drug therapy.

Dr. Kok Siong Chen
Dr. Lucia Moreno-Lama
Dr. Filippo Rossignoli
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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

  • glioma
  • drug therapy
  • glioblastoma
  • targeted treatment
  • blood–brain-barrier

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Published Papers (3 papers)

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Research

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15 pages, 13179 KiB  
Article
Chitosan-Based Polymeric Nanoparticles as an Efficient Gene Delivery System to Cross Blood Brain Barrier: In Vitro and In Vivo Evaluations
by Ishaq N. Khan, Shiza Navaid, Walifa Waqar, Deema Hussein, Najeeb Ullah, Muhammad Umar Aslam Khan, Zakir Hussain and Aneela Javed
Pharmaceuticals 2024, 17(2), 169; https://doi.org/10.3390/ph17020169 - 29 Jan 2024
Cited by 14 | Viewed by 2456
Abstract
Significant progress has been made in the field of gene therapy, but effective treatments for brain tumors remain challenging due to their complex nature. Current treatment options have limitations, especially due to their inability to cross the blood-brain barrier (BBB) and precisely target [...] Read more.
Significant progress has been made in the field of gene therapy, but effective treatments for brain tumors remain challenging due to their complex nature. Current treatment options have limitations, especially due to their inability to cross the blood-brain barrier (BBB) and precisely target cancer cells. Therefore options that are safer, more effective, and capable of specifically targeting cancer cells are urgently required as alternatives. This current study aimed to develop highly biocompatible natural biopolymeric chitosan nanoparticles (CNPs) as potential gene delivery vehicles that can cross the BBB and serve as gene or drug delivery vehicles for brain disease therapeutics. The efficiency of the CNPs was evaluated via in vitro transfection of Green Fluorescent Protein (GFP)-tagged plasmid in HEK293-293 and brain cancer MG-U87 cell lines, as well as within in vivo mouse models. The CNPs were prepared via a complex coacervation method, resulting in nanoparticles of approximately 260 nm in size. In vitro cytotoxicity analysis revealed that the CNPs had better cell viability (85%) in U87 cells compared to the chemical transfection reagent (CTR) (72%). Moreover, the transfection efficiency of the CNPs was also higher, as indicated by fluorescent emission microscopy (20.56% vs. 17.79%) and fluorescent-activated cell sorting (53% vs. 27%). In vivo assays using Balb/c mice revealed that the CNPs could efficiently cross the BBB, suggesting their potential as efficient gene delivery vehicles for targeted therapies against brain cancers as well as other brain diseases for which the efficient targeting of a therapeutic load to the brain cells has proven to be a real challenge. Full article
(This article belongs to the Special Issue Drug Therapy for Glioma)
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12 pages, 2370 KiB  
Article
The Bi-(AID-1-T) G-Quadruplex Has a Janus Effect on Primary and Recurrent Gliomas: Anti-Proliferation and Pro-Migration
by Svetlana Pavlova, Lika Fab, Ekaterina Savchenko, Anastasia Ryabova, Marina Ryzhova, Alexander Revishchin, Igor Pronin, Dmitry Usachev, Alexey Kopylov and Galina Pavlova
Pharmaceuticals 2024, 17(1), 74; https://doi.org/10.3390/ph17010074 - 7 Jan 2024
Cited by 2 | Viewed by 1487
Abstract
High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead [...] Read more.
High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead to recurrent tumors. When developing new treatment approaches, the effect is most often evaluated on standard and phenotypically depleted cancer cell lines. Moreover, there is much focus on the anti-proliferative effect of such therapies without considering the possible stimulation of migratory activity. In this paper, we studied how glioma cell migration changes after exposure to bi-(AID-1-T), an anti-proliferative aptamer. We investigated the effect of this aptamer on eight human glioma cell cultures (Grades III and IV) that were derived from patients’ tumor tissue; the difference between primary and recurrent tumors was taken into account. Despite its strong anti-proliferative activity, bi-(AID-1-T) was shown to induce migration of recurrent tumor cells. This result shows the importance of studying the effect of therapeutic molecules on the invasive properties of glioma tumor cells in order to reduce the likelihood of inducing tumor recurrence. Full article
(This article belongs to the Special Issue Drug Therapy for Glioma)
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Review

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18 pages, 996 KiB  
Review
Isocitrate Dehydrogenase Inhibitors in Glioma: From Bench to Bedside
by Merve Hazal Ser, Mason Webb, Anna Thomsen and Ugur Sener
Pharmaceuticals 2024, 17(6), 682; https://doi.org/10.3390/ph17060682 - 26 May 2024
Viewed by 1900
Abstract
Isocitrate dehydrogenase (IDH) mutant gliomas are a primary malignancy of the central nervous system (CNS) malignancies, most commonly affecting adults under the age of 55. Standard of care therapy for IDH-mutant gliomas involves maximal safe resection, radiotherapy, and chemotherapy. However, despite good initial [...] Read more.
Isocitrate dehydrogenase (IDH) mutant gliomas are a primary malignancy of the central nervous system (CNS) malignancies, most commonly affecting adults under the age of 55. Standard of care therapy for IDH-mutant gliomas involves maximal safe resection, radiotherapy, and chemotherapy. However, despite good initial responses to multimodality treatment, recurrence is virtually universal. IDH-mutant gliomas represent a life-limiting prognosis. For this reason, there is a great need for novel treatments that can prolong survival. Uniquely for IDH-mutant gliomas, the IDH mutation is the direct driver of oncogenesis through its oncometabolite 2-hydroxygluterate. Inhibition of this mutated IDH with a corresponding reduction in 2-hydroxygluterate offers an attractive treatment target. Researchers have tested several IDH inhibitors in glioma through preclinical and early clinical trials. A phase III clinical trial of an IDH1 and IDH2 inhibitor vorasidenib yielded promising results among patients with low-grade IDH-mutant gliomas who had undergone initial surgery and no radiation or chemotherapy. However, many questions remain regarding optimal use of IDH inhibitors in clinical practice. In this review, we discuss the importance of IDH mutations in oncogenesis of adult-type diffuse gliomas and current evidence supporting the use of IDH inhibitors as therapeutic agents for glioma treatment. We also examine unresolved questions and propose potential directions for future research. Full article
(This article belongs to the Special Issue Drug Therapy for Glioma)
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