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

Alomari, Safwan; Zhang, Irma; Hernandez, Adrian F.; Kraft, Caitlin Y.; Raj, Divyaansh; Kedda, Jayanidhi; Tyler, Betty

doi:10.3390/biom11121870

Cited by 30 publications

(13 citation statements)

References 172 publications

(274 reference statements)

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“…Drug repositioning also called as repurpose drugs is a growing concept that explores pre-existing a well-established drug to treat diseases aside from the intended ones. This concept results in lowering the overall developmental cost, time and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities [138]. In case of GSCs, repurpose drugs are being tested and have shown encouraging results.…”

Section: Drugs Targeting Metabolic Pathwaysmentioning

confidence: 99%

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Potential Role of Cancer Stem Cells in Glioblastoma: A Therapeutic Aspect

Tiwari¹,

Sharma²,

Saxena³

2023

Glioblastoma - Current Evidence

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High-grade glioma (HGG) such as glioblastoma multiforme (GBM) is an aggressive brain tumor that is still associated with poor prognosis. With the discovery and advancement in understanding of cancer stem cells (CSC) in glioma, these cells have emerged as seed cells for tumor growth and recurrence and appear as a potential target for therapeutics. Glioma stem cells (GSCs) demonstrate capacity of self-renewal, proliferation, and differentiation into multiple cell types and can contribute to tumor heterogeneity. Their role is established in tumorigenesis, metastasis, chemo- and radio-resistance and appears as a major cause for tumor recurrence. Thus, targeting GSCs by various therapeutics may improve effectiveness of the drugs in use alone or in combination to significantly improve patient survival outcome in GBM cases. In this chapter, we have discussed various mechanisms that drive GSC including signaling pathways and tumor microenvironment. We have also discussed the mechanism behind resistance of GSCs toward therapeutics and the pathways that can be targeted to improve the outcome of the patients.

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Section: Drugs Targeting Metabolic Pathwaysmentioning

confidence: 99%

“…Similarly glimepiride, another anti-diabetes drug, impairs GSCs by targeting glycolytic flux and increases its radio sensitivity to GBM [791]. Further, more repurpose drugs need to be identified that can effectively target GSCs along with its associated mechanism before it can be used in clinical application [138].…”

Section: Drugs Targeting Metabolic Pathwaysmentioning

confidence: 99%

Potential Role of Cancer Stem Cells in Glioblastoma: A Therapeutic Aspect

Tiwari¹,

Sharma²,

Saxena³

2023

Glioblastoma - Current Evidence

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“…In fact, scholars have demonstrated that the BBB in patients with malignant gliomas is frequently damaged to varying degrees. The tolerance of gliomas themselves to anticancer drugs is the most essential cause of chemotherapy failure ( 5 ). Therefore, revealing the mechanisms of resistance is of crucial importance for reducing or eliminating the phenomenon of chemoresistance.…”

Section: Mechanisms Of Chemotherapy Resistance In Gliomasmentioning

confidence: 99%

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

et al. 2022

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As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high-grade gliomas dominated by glioblastoma multiforme (GBM). The prognosis of GBM remains poor despite improvements in treatment modalities, posing a serious threat to human health. At present, although drugs such as temozolomide, cisplatin and bevacizumab, are effective in improving the overall survival of patients with GBM, most patients eventually develop drug resistance, leading to poor clinical prognosis. The development of multidrug resistance has therefore become a major obstacle to improving the effectiveness of chemotherapy for GBM. The ability to fully understand the underlying mechanisms of chemotherapy resistance and to develop novel therapeutic targets to overcome resistance is critical to improving the prognosis of patients with GBM. Of note, growing evidence indicates that a large number of abnormally expressed noncoding RNAs (ncRNAs) have a central role in glioma chemoresistance and may target various mechanisms to modulate chemosensitivity. In the present review, the roles and molecular mechanisms of ncRNAs in glioma drug resistance were systematically summarized, the potential of ncRNAs as drug resistance markers and novel therapeutic targets of glioma were discussed and prospects for glioma treatment were outlined. ncRNAs are a research direction for tumor drug resistance mechanisms and targeted therapies, which not only provides novel perspectives for reversing glioma drug resistance but may also promote the development of precision medicine for clinical diagnosis and treatment.

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“…As a result of these developments, a plethora of approved drugs, initially developed for other malignancies or non-oncological indications, are now being (re)evaluated as potential treatments for GBM patients [ 166 , 194 , 220 , 221 , 222 ]. An overview of previous and ongoing clinical trials assessing repurposed drugs in GBM patients is presented in Table 2 .…”

Section: Drug Repurposing For Glioblastomamentioning

confidence: 99%

Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma

Ntafoulis

Koolen

Leenstra

et al. 2022

Cancers

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Glioblastoma (GBM) remains one of the most difficult tumors to treat. The mean overall survival rate of 15 months and the 5-year survival rate of 5% have not significantly changed for almost 2 decades. Despite progress in understanding the pathophysiology of the disease, no new effective treatments to combine with radiation therapy after surgical tumor debulking have become available since the introduction of temozolomide in 1999. One of the main reasons for this is the scarcity of compounds that cross the blood–brain barrier (BBB) and reach the brain tumor tissue in therapeutically effective concentrations. In this review, we focus on the role of the BBB and its importance in developing brain tumor treatments. Moreover, we discuss drug repurposing, a drug discovery approach to identify potential effective candidates with optimal pharmacokinetic profiles for central nervous system (CNS) penetration and that allows rapid implementation in clinical trials. Additionally, we provide an overview of repurposed candidate drug currently being investigated in GBM at the preclinical and clinical levels. Finally, we highlight the importance of phase 0 trials to confirm tumor drug exposure and we discuss emerging drug delivery technologies as an alternative route to maximize therapeutic efficacy of repurposed candidate drug.

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

Cited by 30 publications

References 172 publications

Potential Role of Cancer Stem Cells in Glioblastoma: A Therapeutic Aspect

Potential Role of Cancer Stem Cells in Glioblastoma: A Therapeutic Aspect

NcRNAs: Multi‑angle participation in the regulation of glioma chemotherapy resistance (Review)

Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma

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