International Journal of Molecular Sciences

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Dear Colleagues,

Glioblastoma is the most common and aggressive primary malignant brain tumor in adult patients. Despite multimodal treatment with maximal safe surgical resection followed by concurrent radio-chemotherapy and adjuvant chemotherapy with temozolomide, prognosis remains poor with a median survival of 1 year. Because glioblastoma treatment remains a highly unmet clinical need, deeper mechanistic insight into the molecular changes present in these tumors is required.

In recent years, a multitude of novel therapies have shown promising signs of efficacy in glioblastoma patients. Precision medicine such as the combination of dabrafenib and trametinib in BRAF-V600E-mutated gliomas, or other tyrosine kinase inhibitors such as regorafenib or NTRK inhibitors, may be used in certain patients. However, in the longer term, an enhanced understanding of the underlying molecular characteristics and genetic landscape of glioblastoma is required to identify novel therapies such as targeted therapies and combination regimens.

This Special Issue is the continuation of our previous Special Issue "New Insights into Glioblastoma: Cellular and Molecular” and will cover all molecular aspects of glioblastoma, including original research on current and experimental treatment options with molecular research and translational work on this cancer’s molecular characteristics. Full reviews and novel communications on these topics are also welcome.

Prof. Dr. Giuseppe Lombardi
Guest Editor

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Published Papers (2 papers)

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Research

16 pages, 4500 KiB

Open AccessArticle

DKK3 Expression in Glioblastoma: Correlations with Biomolecular Markers

by Maria Caffo, Giovanna Casili, Gerardo Caruso, Valeria Barresi, Michela Campolo, Irene Paterniti, Letteria Minutoli, Tamara Ius and Emanuela Esposito

Int. J. Mol. Sci. 2024, 25(7), 4091; https://doi.org/10.3390/ijms25074091 - 07 Apr 2024

Viewed by 483

Abstract

Glioblastoma is the most common malignant primary tumor of the CNS. The prognosis is dismal, with a median survival of 15 months. Surgical treatment followed by adjuvant therapies such as radiotherapy and chemotherapy characterize the classical strategy. The WNT pathway plays a key role in cellular proliferation, differentiation, and invasion. The DKK3 protein, capable of acting as a tumor suppressor, also appears to be able to modulate the WNT pathway. We performed, in a series of 40 patients, immunohistochemical and Western blot evaluations of DKK3 to better understand how the expression of this protein can influence clinical behavior. We used a statistical analysis, with correlations between the expression of DKK3 and overall survival, age, sex, Ki-67, p53, and MGMT and IDH status. We also correlated our data with information included in the cBioPortal database. In our analyses, DKK3 expression, in both immunohistochemistry and Western blot analyses, was reduced or absent in many cases, showing downregulation. To date, no clinical study exists in the literature that reports a potential correlation between IDH and MGMT status and the WNT pathway through the expression of DKK3. Modulation of this pathway through the expression of DKK3 could represent a new tailored therapeutic strategy in the treatment of glioblastoma. Full article

(This article belongs to the Special Issue New Insights into Glioblastoma: Cellular and Molecular 2.0)

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18 pages, 2619 KiB

Open AccessArticle

Glut-3 Gene Knockdown as a Potential Strategy to Overcome Glioblastoma Radioresistance

by Gaia Pucci, Luigi Minafra, Valentina Bravatà, Marco Calvaruso, Giuseppina Turturici, Francesco P. Cammarata, Gaetano Savoca, Boris Abbate, Giorgio Russo, Vincenzo Cavalieri and Giusi I. Forte

Int. J. Mol. Sci. 2024, 25(4), 2079; https://doi.org/10.3390/ijms25042079 - 08 Feb 2024

Viewed by 918

Abstract

The hypoxic pattern of glioblastoma (GBM) is known to be a primary cause of radioresistance. Our study explored the possibility of using gene knockdown of key factors involved in the molecular response to hypoxia, to overcome GBM radioresistance. We used the U87 cell line subjected to chemical hypoxia generated by CoCl2 and exposed to 2 Gy of X-rays, as single or combined treatments, and evaluated gene expression changes of biomarkers involved in the Warburg effect, cell cycle control, and survival to identify the best molecular targets to be knocked-down, among those directly activated by the HIF-1α transcription factor. By this approach, glut-3 and pdk-1 genes were chosen, and the effects of their morpholino-induced gene silencing were evaluated by exploring the proliferative rates and the molecular modifications of the above-mentioned biomarkers. We found that, after combined treatments, glut-3 gene knockdown induced a greater decrease in cell proliferation, compared to pdk-1 gene knockdown and strong upregulation of glut-1 and ldha, as a sign of cell response to restore the anaerobic glycolysis pathway. Overall, glut-3 gene knockdown offered a better chance of controlling the anaerobic use of pyruvate and a better proliferation rate reduction, suggesting it is a suitable silencing target to overcome radioresistance. Full article

(This article belongs to the Special Issue New Insights into Glioblastoma: Cellular and Molecular 2.0)

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