Biomedicines

Research

14 pages, 3252 KiB

Open AccessArticle

An NF-κB- and Therapy-Related Regulatory Network in Glioma: A Potential Mechanism of Action for Natural Antiglioma Agents

by Evrysthenis Vartholomatos, Stefania Mantziou, George A. Alexiou, Diamanto Lazari, Chrissa Sioka, Athanassios Kyritsis and Georgios S. Markopoulos

Biomedicines 2022, 10(5), 935; https://doi.org/10.3390/biomedicines10050935 - 19 Apr 2022

Cited by 7 | Viewed by 1799

Abstract

High-grade gliomas are among the most aggressive malignancies, with significantly low median survival. Recent experimental research in the field has highlighted the importance of natural substances as possible antiglioma agents, also known for their antioxidant and anti-inflammatory action. We have previously shown that [...] Read more.

High-grade gliomas are among the most aggressive malignancies, with significantly low median survival. Recent experimental research in the field has highlighted the importance of natural substances as possible antiglioma agents, also known for their antioxidant and anti-inflammatory action. We have previously shown that natural substances target several surface cluster of differentiation (CD) markers in glioma cells, as part of their mechanism of action. We analyzed the genome-wide NF-κB binding sites residing in consensus regulatory elements, based on ENCODE data. We found that NF-κB binding sites reside adjacent to the promoter regions of genes encoding CD markers targeted by antiglioma agents (namely, CD15/FUT4, CD28, CD44, CD58, CD61/SELL, CD71/TFRC, and CD122/IL2RB). Network and pathway analysis revealed that the markers are associated with a core network of genes that, altogether, participate in processes that associate tumorigenesis with inflammation and immune evasion. Our results reveal a core regulatory network that can be targeted in glioblastoma, with apparent implications in individuals that suffer from this devastating malignancy. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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Review

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19 pages, 1450 KiB

Open AccessReview

Small Molecules and Immunotherapy Agents for Enhancing Radiotherapy in Glioblastoma

by Jennifer K. Matsui, Haley K. Perlow, Alex R. Ritter, Rituraj Upadhyay, Raju R. Raval, Evan M. Thomas, Sasha J. Beyer, Clement Pillainayagam, Justin Goranovich, Shirley Ong, Pierre Giglio and Joshua D. Palmer

Biomedicines 2022, 10(7), 1763; https://doi.org/10.3390/biomedicines10071763 - 21 Jul 2022

Cited by 4 | Viewed by 2891

Abstract

Glioblastoma (GBM) is an aggressive primary brain tumor that is associated with a poor prognosis and quality of life. The standard of care has changed minimally over the past two decades and currently consists of surgery followed by radiotherapy (RT), concomitant and adjuvant [...] Read more.

Glioblastoma (GBM) is an aggressive primary brain tumor that is associated with a poor prognosis and quality of life. The standard of care has changed minimally over the past two decades and currently consists of surgery followed by radiotherapy (RT), concomitant and adjuvant temozolomide, and tumor treating fields (TTF). Factors such as tumor hypoxia and the presence of glioma stem cells contribute to the radioresistant nature of GBM. In this review, we discuss the current treatment modalities, mechanisms of radioresistance, and studies that have evaluated promising radiosensitizers. Specifically, we highlight small molecules and immunotherapy agents that have been studied in conjunction with RT in clinical trials. Recent preclinical studies involving GBM radiosensitizers are also discussed. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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31 pages, 2688 KiB

Open AccessReview

Metal-Based Nanostructured Therapeutic Strategies for Glioblastoma Treatment—An Update

by Agata M. Gawel, Ravi Singh and Waldemar Debinski

Biomedicines 2022, 10(7), 1598; https://doi.org/10.3390/biomedicines10071598 - 5 Jul 2022

Cited by 6 | Viewed by 2714

Abstract

Glioblastoma (GBM) is the most commonly diagnosed and most lethal primary malignant brain tumor in adults. Standard treatments are ineffective, and despite promising results obtained in early phases of experimental clinical trials, the prognosis of GBM remains unfavorable. Therefore, there is need for [...] Read more.

Glioblastoma (GBM) is the most commonly diagnosed and most lethal primary malignant brain tumor in adults. Standard treatments are ineffective, and despite promising results obtained in early phases of experimental clinical trials, the prognosis of GBM remains unfavorable. Therefore, there is need for exploration and development of innovative methods that aim to establish new therapies or increase the effectiveness of existing therapies. One of the most exciting new strategies enabling combinatory treatment is the usage of nanocarriers loaded with chemotherapeutics and/or other anticancer compounds. Nanocarriers exhibit unique properties in antitumor therapy, as they allow highly efficient drug transport into cells and sustained intracellular accumulation of the delivered cargo. They can be infused into and are retained by GBM tumors, and potentially can bypass the blood–brain barrier. One of the most promising and extensively studied groups of nanostructured therapeutics are metal-based nanoparticles. These theranostic nanocarriers demonstrate relatively low toxicity, thus they might be applied for both diagnosis and therapy. In this article, we provide an update on metal-based nanostructured constructs in the treatment of GBM. We focus on the interaction of metal nanoparticles with various forms of electromagnetic radiation for use in photothermal, photodynamic, magnetic hyperthermia and ionizing radiation sensitization applications. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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12 pages, 581 KiB

Open AccessReview

Glioblastoma in the Elderly: Review of Molecular and Therapeutic Aspects

by Francesco Bruno, Alessia Pellerino, Rosa Palmiero, Luca Bertero, Cristina Mantovani, Diego Garbossa, Riccardo Soffietti and Roberta Rudà

Biomedicines 2022, 10(3), 644; https://doi.org/10.3390/biomedicines10030644 - 10 Mar 2022

Cited by 12 | Viewed by 2331

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumour. As GBM incidence is associated with age, elderly people represent a consistent subgroup of patients. Elderly people with GBM show dismal prognosis (about 6 months) and limited response to treatments. Age is a negative [...] Read more.

Glioblastoma (GBM) is the most aggressive primary brain tumour. As GBM incidence is associated with age, elderly people represent a consistent subgroup of patients. Elderly people with GBM show dismal prognosis (about 6 months) and limited response to treatments. Age is a negative prognostic factor, which correlates with clinical frailty, poorer tolerability to surgery or adjuvant radio-chemotherapy, and higher occurrence of comorbidities and/or secondary complications. The aim of this paper is to review the clinical and molecular characteristics, current therapeutic options, and prognostic factors of elderly patients with GBM. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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19 pages, 5666 KiB

Open AccessReview

Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma

by Konstantinos Gousias, Theocharis Theocharous and Matthias Simon

Biomedicines 2022, 10(3), 564; https://doi.org/10.3390/biomedicines10030564 - 28 Feb 2022

Cited by 31 | Viewed by 7111

Abstract

Cells of glioblastoma, the most frequent primary malignant brain tumor, are characterized by their rapid growth and infiltration of adjacent healthy brain parenchyma, which reflects their aggressive biological behavior. In order to maintain their excessive proliferation and invasion, glioblastomas exploit the innate biological [...] Read more.

Cells of glioblastoma, the most frequent primary malignant brain tumor, are characterized by their rapid growth and infiltration of adjacent healthy brain parenchyma, which reflects their aggressive biological behavior. In order to maintain their excessive proliferation and invasion, glioblastomas exploit the innate biological capacities of the patients suffering from this tumor. The pathways involved in cell cycle regulation and apoptosis are the mechanisms most commonly affected. The following work reviews the regulatory pathways of cell growth in general as well as the dysregulated cell cycle and apoptosis relevant mechanisms observed in glioblastomas. We then describe the molecular targeting of the current established adjuvant therapy and present ongoing trials or completed studies on specific promising therapeutic agents that induce cell cycle arrest and apoptosis of glioblastoma cells. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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24 pages, 1149 KiB

Open AccessReview

Immunotherapeutic Approaches for Glioblastoma Treatment

by Nasser K. Yaghi and Mark R. Gilbert

Biomedicines 2022, 10(2), 427; https://doi.org/10.3390/biomedicines10020427 - 11 Feb 2022

Cited by 6 | Viewed by 3552

Abstract

Glioblastoma remains a challenging disease to treat, despite well-established standard-of-care treatments, with a median survival consistently of less than 2 years. In this review, we delineate the unique disease-specific challenges for immunotherapies, both brain-related and non-brain-related, which will need to be adequately overcome [...] Read more.

Glioblastoma remains a challenging disease to treat, despite well-established standard-of-care treatments, with a median survival consistently of less than 2 years. In this review, we delineate the unique disease-specific challenges for immunotherapies, both brain-related and non-brain-related, which will need to be adequately overcome for the development of effective treatments. We also review current immunotherapy treatments, with a focus on clinical applications, and propose future directions for the field of GBM immunotherapy. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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13 pages, 928 KiB

Open AccessReview

Radiosensitization and Radioprotection by Curcumin in Glioblastoma and Other Cancers

by Vasiliki Zoi, Vasiliki Galani, Pericles Tsekeris, Athanasios P. Kyritsis and George A. Alexiou

Biomedicines 2022, 10(2), 312; https://doi.org/10.3390/biomedicines10020312 - 28 Jan 2022

Cited by 22 | Viewed by 3691

Abstract

Radiation therapy plays an important role in almost every cancer treatment. However, radiation toxicity to normal tissues, mainly due to the generation of reactive free radicals, has limited the efficacy of radiotherapy in clinical practice. Curcumin has been reported to possess significant antitumor [...] Read more.

Radiation therapy plays an important role in almost every cancer treatment. However, radiation toxicity to normal tissues, mainly due to the generation of reactive free radicals, has limited the efficacy of radiotherapy in clinical practice. Curcumin has been reported to possess significant antitumor properties. Although curcumin can sensitize cancer cells to irradiation, healthy cells are much less sensitive to this effect, and thus, curcumin is thought to be a potent, yet safe anti-cancer agent. In this review, a summary of the role of curcumin as both a radiosensitizer and radioprotector has been presented, based on the most recent data from the experimental and clinical evaluation of curcumin in different cancer cell lines, animal models, and human patients. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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Other

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7 pages, 225 KiB

Open AccessOpinion

The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?

by Kostas A. Papavassiliou and Athanasios G. Papavassiliou

Biomedicines 2021, 9(12), 1809; https://doi.org/10.3390/biomedicines9121809 - 1 Dec 2021

Cited by 5 | Viewed by 1850

Abstract

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway [...] Read more.

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implicated in GBM pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to target the mTOR pathway with first-generation mTOR inhibitors appeared promising in the preclinical stage; however, results have been disappointing in clinical trials, owing to the heterogeneous nature of GBM, escape mechanisms against treatment, the blood–brain barrier, drug-related toxicities, and the imperfect design of clinical trials, among others. The development of next-generation mTOR inhibitors and their current evaluation in clinical trials have sparked new hope to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies are continuously furthering our understanding of mTOR signaling dysregulation, its downstream effects, and interplay with other signaling pathways in GBM tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will eventually prove to be fruitful or futile. Full article

(This article belongs to the Special Issue Potent Agent Research for Glioblastoma Treatment)

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