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Cancers
Special Issues
Repositioning Drugs for Cancer Gliomas
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Repositioning Drugs for Cancer Gliomas

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 10809

Special Issue Editors

Prof. Kumlesh Kumar Dev

E-Mail Website
Guest Editor
School of Medicine, Trinity College Dublin, Dublin, Ireland
Interests: neuroscience; glia; astrocytes; myelination; drug development; drug repositioning
Dr. Melissa J. Conroy

E-Mail Website
Co-Guest Editor
Department of Physiology, School of Medicine, Trinity College Dublin, Ireland
Interests: immunology; cancer; inflammation; immunotherapy; lymphocytes; chemokines

Special Issue Information

Dear Colleagues,

Gliomas account for more than 70% of malignant brain tumors. Archetypal glial tumors known to involve glial cell dysregulation include: (i) astrocytomas, the most common glioma developing from astrocytes, (ii) oligodendrogliomas, derived from oligodendrocytes and (iii) glioblastoma multiforme, the most invasive/aggressive brain cancer involving astrocytes and oligodendrocytes.

Unfortunately, these cancers are poorly served by therapeutic treatment. This remains the case, despite astrocytes and oligodendrocytes being well studied, with existing marketed drugs known alter their cell function by engagement of the receptors these cells express.

We consider that the repositioning of current marketed drugs or drugs in development known to regulate astrocyte or oligodendrocyte biology, or by drugs known to regulate receptors expressed on these glial cells are worthy of study in astrocytomas, oligodendrogliomas and glioblastoma multiforme.

In this Special Issue of Cancers, here coin and introduce the phrase Redcangliomics (repositioning drugs for cancer gliomas) and cover new research articles and timely reviews on therpies that regulate astrocyte and oligodendrocyte biology and that have potential utility in the management of patients with the cancers associated with astrocytes and oligodendrocytes.

Prof. Kumlesh Kumar Dev
Dr. Melissa J. Conroy
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. Cancers 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 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

  • Receptors
  • Pharmacology
  • Gliomas
  • Astrocytes
  • Oligodendrocytes
  • Checkpoint Inhibitors
  • Drug Repositioning

Published Papers (4 papers)

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Research

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25 pages, 6562 KiB  
Article
Exploring Novel Therapeutic Opportunities for Glioblastoma Using Patient-Derived Cell Cultures
by Iwona A. Ciechomska, Kamil Wojnicki, Bartosz Wojtas, Paulina Szadkowska, Katarzyna Poleszak, Beata Kaza, Kinga Jaskula, Wiktoria Dawidczyk, Ryszard Czepko, Mariusz Banach, Bartosz Czapski, Pawel Nauman, Katarzyna Kotulska, Wieslawa Grajkowska, Marcin Roszkowski, Tomasz Czernicki, Andrzej Marchel and Bozena Kaminska
Cancers 2023, 15(5), 1562; https://doi.org/10.3390/cancers15051562 - 2 Mar 2023
Cited by 5 | Viewed by 2390
Abstract
Glioblastomas (GBM) are the most common, primary brain tumors in adults. Despite advances in neurosurgery and radio- and chemotherapy, the median survival of GBM patients is 15 months. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and molecular heterogeneity of [...] Read more.
Glioblastomas (GBM) are the most common, primary brain tumors in adults. Despite advances in neurosurgery and radio- and chemotherapy, the median survival of GBM patients is 15 months. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and molecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have established 13 GBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNA-seq, immunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1R132H, TP53 and PDGFRα), classical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), and the expression of pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, β-Tubulin III) markers revealed the striking intertumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-CADHERIN and CD44 at the mRNA/protein levels suggested increased epithelial-to-mesenchymal transition (EMT) in most studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-derived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated cultures, the strongest accumulation of the apoptotic markers caspase 7 and PARP were found in WG4 cells with methylated MGMT, suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-derived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream signaling pathways. AG1478 caused decreased levels of phospho-STAT3, and thus inhibition of active STAT3 augmented antitumor effects of DOX and TMZ in cells with methylated and intermediate status of MGMT. Altogether, our findings show that GBM-derived cell cultures mimic the considerable tumor heterogeneity, and that identifying patient-specific signaling vulnerabilities can assist in overcoming therapy resistance, by providing personalized combinatorial treatment recommendations. Full article
(This article belongs to the Special Issue Repositioning Drugs for Cancer Gliomas)
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Review

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23 pages, 13107 KiB  
Review
Advanced Magnetic Resonance Imaging in the Evaluation of Treated Glioblastoma: A Pictorial Essay
by Matia Martucci, Rosellina Russo, Carolina Giordano, Chiara Schiarelli, Gabriella D’Apolito, Laura Tuzza, Francesca Lisi, Giuseppe Ferrara, Francesco Schimperna, Stefania Vassalli, Rosalinda Calandrelli and Simona Gaudino
Cancers 2023, 15(15), 3790; https://doi.org/10.3390/cancers15153790 - 26 Jul 2023
Cited by 2 | Viewed by 1273
Abstract
MRI plays a key role in the evaluation of post-treatment changes, both in the immediate post-operative period and during follow-up. There are many different treatment’s lines and many different neuroradiological findings according to the treatment chosen and the clinical timepoint at which MRI [...] Read more.
MRI plays a key role in the evaluation of post-treatment changes, both in the immediate post-operative period and during follow-up. There are many different treatment’s lines and many different neuroradiological findings according to the treatment chosen and the clinical timepoint at which MRI is performed. Structural MRI is often insufficient to correctly interpret and define treatment-related changes. For that, advanced MRI modalities, including perfusion and permeability imaging, diffusion tensor imaging, and magnetic resonance spectroscopy, are increasingly utilized in clinical practice to characterize treatment effects more comprehensively. This article aims to provide an overview of the role of advanced MRI modalities in the evaluation of treated glioblastomas. For a didactic purpose, we choose to divide the treatment history in three main timepoints: post-surgery, during Stupp (first-line treatment) and at recurrence (second-line treatment). For each, a brief introduction, a temporal subdivision (when useful) or a specific drug-related paragraph were provided. Finally, the current trends and application of radiomics and artificial intelligence (AI) in the evaluation of treated GB have been outlined. Full article
(This article belongs to the Special Issue Repositioning Drugs for Cancer Gliomas)
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22 pages, 2442 KiB  
Review
Existing Evidence for the Repurposing of PARP-1 Inhibitors in Rare Demyelinating Diseases
by Marianna Mekhaeil, Kumlesh Kumar Dev and Melissa Jane Conroy
Cancers 2022, 14(3), 687; https://doi.org/10.3390/cancers14030687 - 29 Jan 2022
Cited by 11 | Viewed by 3385
Abstract
Over the past decade, Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. Therapies targeting the enzyme, PARP-1, have since established their place as maintenance drugs for cancer. [...] Read more.
Over the past decade, Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have arisen as a novel and promising targeted therapy for breast cancer gene (BRCA)-mutated ovarian and breast cancer patients. Therapies targeting the enzyme, PARP-1, have since established their place as maintenance drugs for cancer. Here, we present existing evidence that implicates PARP-1 as a player in the development and progression of both malignancy and demyelinating disease. These findings, together with the proven clinical efficacy and marketed success of PARP-1 inhibitors in cancer, present the repurposing of these drugs for demyelinating diseases as a desirable therapeutic concept. Indeed, PARP-1 inhibitors are noted to demonstrate neuroprotective effects in demyelinating disorders such as multiple sclerosis and Parkinson’s disease, further supporting the use of these drugs in demyelinating, neuroinflammatory, and neurodegenerative diseases. In this review, we discuss the potential for repurposing PARP-1 inhibitors, with a focus on rare demyelinating diseases. In particular, we address the possible use of PARP-1 inhibitors in examples of rare leukodystrophies, for which there are a paucity of treatment options and an urgent need for novel therapeutic approaches. Full article
(This article belongs to the Special Issue Repositioning Drugs for Cancer Gliomas)
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Other

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19 pages, 638 KiB  
Systematic Review
From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review
by Luca Paun, Alessandro Moiraghi, Gianpaolo Jannelli, Aria Nouri, Francesco DiMeco, Johan Pallud, Torstein R. Meling, Shahan Momjian, Karl Schaller, Francesco Prada and Denis Migliorini
Cancers 2021, 13(22), 5614; https://doi.org/10.3390/cancers13225614 - 10 Nov 2021
Cited by 11 | Viewed by 2860
Abstract
Background: Focused Ultrasound (FUS) is gaining a therapeutic role in neuro-oncology considering its novelty and non-invasiveness. Multiple pre-clinical studies show the efficacy of FUS mediated ablation and Blood-Brain Barrier (BBB) opening in high-grade glioma (HGG), but there is still poor evidence in humans, [...] Read more.
Background: Focused Ultrasound (FUS) is gaining a therapeutic role in neuro-oncology considering its novelty and non-invasiveness. Multiple pre-clinical studies show the efficacy of FUS mediated ablation and Blood-Brain Barrier (BBB) opening in high-grade glioma (HGG), but there is still poor evidence in humans, mainly aimed towards assessing FUS safety. Methods: With this systematic review our aim is, firstly, to summarize how FUS is proposed for human HGG treatment. Secondly, we focus on future perspectives and new therapeutic options. Using PRISMA 2020 guidelines, we reviewed case series and trials with description of patient characteristics, pre- and post-operative treatments and FUS outcomes. We considered nine case series (five about tumor ablation and four about BBB opening) with FUS-treated HGG patients between 1991 and 2021. Results: Sixty-eight patients were considered in total, mostly males (67.6%), with a mean age of 50.5 ± 15.3 years old. Major complication rates were found in the tumor ablation group (26.1%). FUS has been rarely applied for direct tumoral ablation in human HGG patients with controversial results, but at the best of current studies, FUS-mediated BBB opening is showing good results with very low complication rates, paving the way for a new reliable technique to improve local chemotherapy delivery and antitumoral immune response. Conclusions: FUS can become a complementary technique to surgical resection and standard radiochemotherapy in recurrent HGG. Ongoing trials could provide in the near future more data on FUS-mediated BBB opening impact on progression-free survival, overall survival and potential drug-delivery capacities. Full article
(This article belongs to the Special Issue Repositioning Drugs for Cancer Gliomas)
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