Glioblastoma: Advances in Molecular Insights and Therapeutic Strategies

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

Deadline for manuscript submissions: closed (10 April 2024) | Viewed by 1387

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Guest Editor
Department of Biomedicine, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark
Interests: glioblastoma

Special Issue Information

Dear Colleagues,

Glioblastoma (GBM) still remains as the deadliest malignant type of primary astrocytoma with an extremely poor prognosis. The standard of care for GBM typically involves surgical resection followed by radiotherapy concomitant with chemotherapy and temozolomide. New molecular insights into multiple aspects of gliomagenesis and significant advances in the treatment of GBM have been achieved in recent decades. Despite these advances, recurrence is almost always certain in GBM, which paves the way to its dismal prognosis. A wide range of factors contribute towards GBM aggressiveness, including, but not limited to, its complex microenvironment, tumor heterogeneity, glioblastoma stem cells (GBSCs), and the presence of the blood–brain barrier (BBB). Several new advances have also been made in conventional treatment strategies involving surgery, radiotherapy, and chemotherapy, as well as in newer treatment approaches like gene therapy, immunotherapy, nanotherapy, phototherapy, etc.

This Special Issue of Cancers aims to invite original research articles or review articles covering the above-mentioned topics or that provide new potential promising insights into GBM biology and treatment.

Dr. Justin V. Joseph
Guest Editor

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Published Papers (2 papers)

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13 pages, 1588 KiB  
Article
Antiretroviral Drug Repositioning for Glioblastoma
by Sarah R. Rivas, Mynor J. Mendez Valdez, Jay S. Chandar, Jelisah F. Desgraves, Victor M. Lu, Leo Ampie, Eric B. Singh, Deepa Seetharam, Christian K. Ramsoomair, Anna Hudson, Shreya M. Ingle, Vaidya Govindarajan, Tara T. Doucet-O’Hare, Catherine DeMarino, John D. Heiss, Avindra Nath and Ashish H. Shah
Cancers 2024, 16(9), 1754; https://doi.org/10.3390/cancers16091754 - 30 Apr 2024
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Abstract
Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in [...] Read more.
Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in multiple cancers; however, its efficacy in GBM remains unclear. To better understand the pleiotropic anticancer effects of ART on GBM, we conducted a comprehensive drug repurposing analysis of ART in GBM to highlight its utility in translational neuro-oncology. To uncover the anticancer role of ART in GBM, we conducted a comprehensive bioinformatic and in vitro screen of antiretrovirals against glioblastoma. Using the DepMap repository and reversal of gene expression score, we conducted an unbiased screen of 16 antiretrovirals in 40 glioma cell lines to identify promising candidates for GBM drug repositioning. We utilized patient-derived neurospheres and glioma cell lines to assess neurosphere viability, proliferation, and stemness. Our in silico screen revealed that several ART drugs including reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) demonstrated marked anti-glioma activity with the capability of reversing the GBM disease signature. RTIs effectively decreased cell viability, GBM stem cell markers, and proliferation. Our study provides mechanistic and functional insight into the utility of ART repurposing for malignant gliomas, which supports the current literature. Given their safety profile, preclinical efficacy, and neuropenetrance, ARTs may be a promising adjuvant treatment for GBM. Full article
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13 pages, 1103 KiB  
Review
Antisense Oligonucleotides for Rapid Translation of Gene Therapy in Glioblastoma
by Jelisah F. Desgraves, Mynor J. Mendez Valdez, Jay Chandar, Muhammet Enes Gurses, Lisa Henderson, Jesus R. Castro, Deepa Seetheram, Michael E. Ivan, Ricardo J. Komotar and Ashish H. Shah
Cancers 2024, 16(10), 1944; https://doi.org/10.3390/cancers16101944 - 20 May 2024
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Abstract
Purpose: The limited efficacy of current treatments for malignant brain tumors necessitates novel therapeutic strategies. This study aimed to assess the potential of antisense oligonucleotides (ASOs) as adjuvant therapy for high-grade gliomas, focusing on their CNS penetration and clinical translation prospects. Methods: A [...] Read more.
Purpose: The limited efficacy of current treatments for malignant brain tumors necessitates novel therapeutic strategies. This study aimed to assess the potential of antisense oligonucleotides (ASOs) as adjuvant therapy for high-grade gliomas, focusing on their CNS penetration and clinical translation prospects. Methods: A comprehensive review of the existing literature was conducted to evaluate the implications of ASOs in neuro-oncology. Studies that investigated ASO therapy’s efficacy, CNS penetration, and safety profile were analyzed to assess its potential as a therapeutic intervention for high-grade gliomas. Results: ASOs present a promising avenue for enhancing targeted gene therapies in malignant gliomas. Their potent CNS penetration, in vivo durability, and efficient transduction offer advantages over conventional treatments. Preliminary in vivo and in vitro studies suggest ASOs as a viable adjuvant therapy for high-grade gliomas, warranting further exploration in clinical trials. Conclusions: ASOs hold significant promise as adjuvant therapy for high-grade gliomas, offering improved CNS penetration and durability compared with existing treatments. While preliminary studies are encouraging, additional research is needed to establish the safety and efficacy of ASO therapy in clinical settings. Further investigation and clinical trials are warranted to validate ASOs as a transformative approach in neuro-oncology. Full article
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