International Journal of Molecular Sciences

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Novel Biomarkers and Molecular Targets in Gliomas

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Dear Colleagues,

The molecular aspect influences the modern classification and treatment strategies for gliomas. It is the constant fascinating research that opens new therapeutic and diagnostic possibilities. This Special Issue aims to highlight the efforts of researchers in identifying and characterizing new molecular markers in order to guide increasingly effective diagnostic and therapeutic strategies in the fight against gliomas.

Therefore, it is our pleasure to invite investigators to contribute original research articles as well as review to this Special Issue that is aimed at promoting the diffusion of the current knowledge of the molecular basis of neuro-oncology. We are particularly interested in articles that provide new insights into pathophysiological mechanisms, which could be used to achieve original diagnostic and therapeutic approaches.

Potential topics include, but are not limited to, the following:

Molecular insights into glioblastoma and the intrinsic brain tumor pathogenesis;
The clinical and surgical translations of the latest pathophysiological findings;
Molecular prognostic factors in glioblastoma and intrinsic brain tumors;
Nutraceuticals and brain tumors;
Autophagy related to the biology of gliomas;
Micro-RNA in the pathogenesis of glial brain tumors;
Cytoskeletal proteins as glioblastoma;
The ultrastructural biomarkers of glial brain tumors;
Molecular targeted therapy for gliomas;
Gene therapy for gliomas.

Dr. Placido Bruzzaniti
Dr. Pietro Familiari
Guest Editors

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20 pages, 2434 KiB

Open AccessReview

Advancements in Telomerase-Targeted Therapies for Glioblastoma: A Systematic Review

by Giovanni Pennisi, Placido Bruzzaniti, Benedetta Burattini, Giacomo Piaser Guerrato, Giuseppe Maria Della Pepa, Carmelo Lucio Sturiale, Pierfrancesco Lapolla, Pietro Familiari, Biagia La Pira, Giancarlo D’Andrea, Alessandro Olivi, Quintino Giorgio D’Alessandris and Nicola Montano

Int. J. Mol. Sci. 2024, 25(16), 8700; https://doi.org/10.3390/ijms25168700 - 9 Aug 2024

Cited by 3 | Viewed by 2660

Abstract

Glioblastoma (GBM) is a primary CNS tumor that is highly lethal in adults and has limited treatment options. Despite advancements in understanding the GBM biology, the standard treatment for GBM has remained unchanged for more than a decade. Only 6.8% of patients survive beyond five years. Telomerase, particularly the hTERT promoter mutations present in up to 80% of GBM cases, represents a promising therapeutic target due to its role in sustaining telomere length and cancer cell proliferation. This review examines the biology of telomerase in GBM and explores potential telomerase-targeted therapies. We conducted a systematic review following the PRISMA-P guidelines in the MEDLINE/PubMed and Scopus databases, from January 1995 to April 2024. We searched for suitable articles by utilizing the terms “GBM”, “high-grade gliomas”, “hTERT” and “telomerase”. We incorporated studies addressing telomerase-targeted therapies into GBM studies, excluding non-English articles, reviews, and meta-analyses. We evaluated a total of 777 records and 46 full texts, including 36 studies in the final review. Several compounds aimed at inhibiting hTERT transcription demonstrated promising preclinical outcomes; however, they were unsuccessful in clinical trials owing to intricate regulatory pathways and inadequate pharmacokinetics. Direct hTERT inhibitors encountered numerous obstacles, including a prolonged latency for telomere shortening and the activation of the alternative lengthening of telomeres (ALT). The G-quadruplex DNA stabilizers appeared to be potential indirect inhibitors, but further clinical studies are required. Imetelstat, the only telomerase inhibitor that has undergone clinical trials, has demonstrated efficacy in various cancers, but its efficacy in GBM has been limited. Telomerase-targeted therapies in GBM is challenging due to complex hTERT regulation and inadequate inhibitor pharmacokinetics. Our study demonstrates that, despite promising preclinical results, no Telomerase inhibitors have been approved for GBM, and clinical trials have been largely unsuccessful. Future strategies may include Telomerase-based vaccines and multi-target inhibitors, which may provide more effective treatments when combined with a better understanding of telomere dynamics and tumor biology. These treatments have the potential to be integrated with existing ones and to improve the outcomes for patients with GBM. Full article

(This article belongs to the Special Issue Novel Biomarkers and Molecular Targets in Gliomas)

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