Role of dimethyl fumarate in the treatment of glioblastoma multiforme: A review article

Ahmadi‐Beni, Reza; Najafi, Ali; Savar, Seyed Mehrdad; Mohebbi, Niayesh; Khoshnevisan, Alireza

doi:10.18502/ijnl.v18i3.1636

Cited by 9 publications

(6 citation statements)

References 59 publications

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“…HGG is considered a challenging subtype of brain tumors with a poor prognosis, aggressive features and lack of targeted therapies. Although many efforts have been made to develop effective treatments, tumor heterogeneity and unknown contexts remain limitations of discovered therapies [ 15 ]. Identification of the key genes and pathways involved in HGG pathogenesis is of particular importance to develop new therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas

2022

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Background Lack of knowledge around underlying mechanisms of gliomas mandates intense research efforts to improve the disease outcomes. Identification of high-grade gliomas pathogenesis which is known for poor prognosis and low survival is of particular importance. Distinguishing the differentially expressed genes is one of the core approaches to clarify the causative factors. Methods Microarray datasets of the treatment-naïve gliomas were provided from the Gene Expression Omnibus considering the similar platform and batch effect removal. Interacting recovery of the top differentially expressed genes was performed on the STRING and Cytoscape platforms. Kaplan–Meier analysis was piloted using RNA sequencing data and the survival rate of glioma patients was checked considering selected genes. To validate the bioinformatics results, the gene expression was elucidated by real-time RT-qPCR in a series of low and high-grade fresh tumor samples. Results We identified 323 up-regulated and 253 down-regulated genes. The top 20 network analysis indicated that PTX3, TIMP1, CHI3L1, LTF and IGFBP3 comprise a crucial role in gliomas progression. The survival was inversely linked to the levels of all selected genes. Further analysis of RNA sequencing data indicated a significant increase in all five genes in high-grade tumors. Among them, PTX3, TIMP1 and LTF did not show any change in low-grade versus controls. Real-time RT-qPCR confirmed the in-silico results and revealed significantly higher expression of selected genes in high-grade samples compared to low-grade. Conclusions Our results highlighted the role of PTX3 and TIMP1 which were previously considered in glioma tumorigenesis as well as LTF as a new potential biomarker.

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Section: Discussionmentioning

confidence: 99%

An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas

2022

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“…Dimethyl fumarate is used in the management of relapsing-remitting multiple sclerosis and psoriasis [ 15 , 70 ]. The drug reduces inflammation and suppresses immune cell function [ 15 ].…”

Section: Drugs Under Clinical Investigationmentioning

confidence: 99%

Drug Repurposing for Glioblastoma and Current Advances in Drug Delivery—A Comprehensive Review of the Literature

et al. 2021

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with an extremely poor prognosis. There is a dire need to develop effective therapeutics to overcome the intrinsic and acquired resistance of GBM to current therapies. The process of developing novel anti-neoplastic drugs from bench to bedside can incur significant time and cost implications. Drug repurposing may help overcome that obstacle. A wide range of drugs that are already approved for clinical use for the treatment of other diseases have been found to target GBM-associated signaling pathways and are being repurposed for the treatment of GBM. While many of these drugs are undergoing pre-clinical testing, others are in the clinical trial phase. Since GBM stem cells (GSCs) have been found to be a main source of tumor recurrence after surgery, recent studies have also investigated whether repurposed drugs that target these pathways can be used to counteract tumor recurrence. While several repurposed drugs have shown significant efficacy against GBM cell lines, the blood–brain barrier (BBB) can limit the ability of many of these drugs to reach intratumoral therapeutic concentrations. Localized intracranial delivery may help to achieve therapeutic drug concentration at the site of tumor resection while simultaneously minimizing toxicity and side effects. These strategies can be considered while repurposing drugs for GBM.

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“…Preclinical studies in tumor models have also shown significant antitumor activity of DMF, which has been linked to its ability to activate Nrf2 and inhibit the NF-κB pathways [214,215] . Promising results have been observed with DMF in several types of cancer models such as glioblastoma, breast cancer, KRAS mutated cancers and myelogenous leukemia [216][217][218][219] . However, to our knowledge, the efficacy of DMF in prostate cancer patients, and especially, its ability to suppress CRPC progression has not been investigated so far.…”

Section: Repurposed Agentsmentioning

confidence: 99%

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

Mondal¹,

Narwani²,

Notta³

et al. 2020

CDR

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Androgen deprivation therapy (ADT) is the mainstay regimen in patients with androgen-dependent prostate cancer (PCa). However, the selection of androgen-independent cancer cells leads to castrate resistant prostate cancer (CRPC). The aggressive phenotype of CRPC cells underscores the need to elucidate mechanisms and therapeutic strategies to suppress CRPC outgrowth. Despite ADT, the activation of androgen receptor (AR) transcription factor continues via crosstalk with parallel signaling pathways. Understanding of how these signaling cascades are initiated and amplified post-ADT is lacking. Hormone deprivation can increase oxidative stress and the resultant reactive oxygen species (ROS) may activate both AR and non-AR signaling. Moreover, ROS-induced inflammatory cytokines may further amplify these redox signaling pathways to augment AR function. However, clinical trials using ROS quenching small molecule antioxidants have not suppressed CRPC progression, suggesting that more potent and persistent suppression of redox signaling in CRPC cells will be needed. The transcription factor Nrf2 increases the expression of numerous antioxidant enzymes and downregulates the function of inflammatory transcription factors, e.g., nuclear factor kappa B. We documented that Nrf2 overexpression can suppress AR-mediated transcription in CRPC cell lines. Furthermore, two Nrf2 activating agents, sulforaphane (a phytochemical) and bardoxolone-methyl (a drug in clinical trial) suppress AR levels and sensitize CRPC cells to anti-androgens. These observations implicate the benefits of potent Nrf2-activators to suppress the lethal signaling cascades that lead to CRPC outgrowth. This review article will address the redox signaling networks that augment AR signaling during PCa progression to CRPC, and the possible utility of Nrf2-activating agents as an adjunct to ADT.

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Role of dimethyl fumarate in the treatment of glioblastoma multiforme: A review article

Cited by 9 publications

References 59 publications

An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas

An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas

Drug Repurposing for Glioblastoma and Current Advances in Drug Delivery—A Comprehensive Review of the Literature

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators

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