Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance

D’Amico, Maria; Amicis, Francesca De

doi:10.20517/cdr.2022.46

Cited by 9 publications

(4 citation statements)

References 109 publications

(198 reference statements)

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“…In turn, high total NOTCH1 immunostaining is associated with progression of kidney renal clear cell carcinoma contradicting TCGA prediction (103,104). Likewise, in contrast to TCGA data, literature suggests association of NOTCH1 expression and glioma progression by modulating CXCL12/CXCR4 (105,124).…”

Section: Expression Of Molecules Involved In the Ctc Cluster Formatio...mentioning

confidence: 79%

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Rozenberg

Buzdin²,

Mohammad³

et al. 2023

Front. Immunol.

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Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.

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Section: Expression Of Molecules Involved In the Ctc Cluster Formatio...mentioning

confidence: 79%

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Rozenberg

Buzdin²,

Mohammad³

et al. 2023

Front. Immunol.

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“…The leading mechanism of resistance in glioma cells is the high activity of O-6-methylguanine DNA methyltransferase (MGMT), which repairs TMZ-induced DNA damage and contributes to TMZ resistance [ 100 ]. TMZ resistance in GBM has also been linked to a number of cellular signalling pathways, including Hedgehog (HH) [ 101 ], NF-κB [ 102 ], Wnt/β-catenin (Wnt) [ 103 ], and Notch [ 104 ].…”

Section: Mechanisms Of Drug Resistance In Glioblastomamentioning

confidence: 99%

Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours—A Research Hypothesis

Żwierełło

Maruszewska

Skórka-Majewicz

et al. 2023

IJMS

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The purpose of this review is to attempt to outline the potential role of fluoride in the pathogenesis of brain tumours, including glioblastoma (GBM). In this paper, we show for the first time that fluoride can potentially affect the generally accepted signalling pathways implicated in the formation and clinical course of GBM. Fluorine compounds easily cross the blood–brain barrier. Enhanced oxidative stress, disruption of multiple cellular pathways, and microglial activation are just a few examples of recent reports on the role of fluoride in the central nervous system (CNS). We sought to present the key mechanisms underlying the development and invasiveness of GBM, as well as evidence on the current state of knowledge about the pleiotropic, direct, or indirect involvement of fluoride in the regulation of these mechanisms in various tissues, including neural and tumour tissue. The effects of fluoride on the human body are still a matter of controversy. However, given the growing incidence of brain tumours, especially in children, and numerous reports on the effects of fluoride on the CNS, it is worth taking a closer look at these mechanisms in the context of brain tumours, including gliomas.

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“…Furthermore, mutations in the WNT pathway’s key components dramatically regulate the WNT pathway. According to one study, the miR-138-2-3p and miR-770-5p are widely expressed in GBM and play an important role in Wnt signaling abnormalities in GBM, but they can also affect -catenin expression in cancers such as hepatocellular carcinoma and laryngeal tumors [ 112 ].…”

Section: Pathways Associated With Glioma and Glioblastomamentioning

confidence: 99%

Progress in Glioma Stem Cell Research

Ramar,

Guo,

Hudson

et al. 2023

Cancers

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Glioblastoma multiforme (GBM) represents a diverse spectrum of primary tumors notorious for their resistance to established therapeutic modalities. Despite aggressive interventions like surgery, radiation, and chemotherapy, these tumors, due to factors such as the blood–brain barrier, tumor heterogeneity, glioma stem cells (GSCs), drug efflux pumps, and DNA damage repair mechanisms, persist beyond complete isolation, resulting in dismal outcomes for glioma patients. Presently, the standard initial approach comprises surgical excision followed by concurrent chemotherapy, where temozolomide (TMZ) serves as the foremost option in managing GBM patients. Subsequent adjuvant chemotherapy follows this regimen. Emerging therapeutic approaches encompass immunotherapy, including checkpoint inhibitors, and targeted treatments, such as bevacizumab, aiming to exploit vulnerabilities within GBM cells. Nevertheless, there exists a pressing imperative to devise innovative strategies for both diagnosing and treating GBM. This review emphasizes the current knowledge of GSC biology, molecular mechanisms, and associations with various signals and/or pathways, such as the epidermal growth factor receptor, PI3K/AKT/mTOR, HGFR/c-MET, NF-κB, Wnt, Notch, and STAT3 pathways. Metabolic reprogramming in GSCs has also been reported with the prominent activation of the glycolytic pathway, comprising aldehyde dehydrogenase family genes. We also discuss potential therapeutic approaches to GSC targets and currently used inhibitors, as well as their mode of action on GSC targets.

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Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance

Cited by 9 publications

References 109 publications

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers

Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours—A Research Hypothesis

Progress in Glioma Stem Cell Research

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