Emerging Therapies for Glioblastoma

Cancers, Год журнала: 2024, Номер 16(8), С. 1485 - 1485

Опубликована: Апрель 12, 2024

Glioblastoma is most commonly a primary brain tumor and the utmost malignant one, with survival rate of approximately 12–18 months. highly heterogeneous, demonstrating that different types cells from same can manifest distinct gene expression patterns biological behaviors. Conventional therapies such as temozolomide, radiation, surgery have limitations. As now, there no cure for glioblastoma. Alternative treatment methods to eradicate glioblastoma are discussed in this review, including targeted PI3K, NFKβ, JAK-STAT, CK2, WNT, NOTCH, Hedgehog, TGFβ pathways. The novel application oncolytic viruses nanomaterials combating also discussed. Despite scores clinical trials glioblastoma, prognosis remains poor. Progress breaching blood–brain barrier avenues combination treatments hold promise future development efficacious therapies.

Язык: Английский

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The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma

Epigenomics, Год журнала: 2025, Номер 17(2), С. 125 - 140

Опубликована: Янв. 19, 2025

Gliomas, highly aggressive tumors of the central nervous system, present overwhelming challenges due to their heterogeneity and therapeutic resistance. Glioblastoma multiforme (GBM), most malignant form, underscores this clinical urgency dismal prognosis despite treatment regimens. Recent advances in cancer research revealed signaling pathways epigenetic mechanisms that intricately govern glioma progression, offering multifaceted targets for intervention. This review explores dynamic interplay between events regulation context glioma, with a particular focus on crucial roles played by non-coding RNAs (ncRNAs). Through direct indirect targeting, ncRNAs emerge as key regulators shaping molecular landscape glioblastoma across its various stages. By dissecting these intricate regulatory networks, novel patient-tailored strategies could be devised improve patient outcomes devastating disease.

Язык: Английский

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YAP/TAZ-associated cell signaling – at the crossroads of cancer and neurodevelopmental disorders

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Янв. 28, 2025

YAP/TAZ (Yes-associated protein/paralog transcriptional co-activator with PDZ-binding domain) are cofactors that the key and major downstream effectors of Hippo signaling pathway. Both known to play a crucial role in defining cellular outcomes, including cell differentiation, proliferation, apoptosis. Aside from canonical cascade components MST1/2 (mammalian STE20-like kinase 1/2), SAV1 (Salvador homologue 1), MOB1A/B (Mps one binder activator 1A/B) LATS1/2 (large tumor suppressor 1/2) upstream YAP/TAZ, activation is also influenced by numerous other pathways. Such non-canonical regulation includes well-known growth factor pathways such as epidermal receptor (EGFR)/ErbB family, Notch, Wnt well cell-cell adhesion, cell-matrix interactions mechanical cues cell’s microenvironment. This puts at center complex network capable regulating developmental processes tissue regeneration. On hand, dysregulation has been implicated diseases various cancers neurodevelopmental disorders. Indeed, recent years, parallels between cancer development disorders have become apparent being these review discusses brain development, special focus on interconnection different conditions.

Язык: Английский

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Regulation of cancer stem cells and immunotherapy of glioblastoma (Review)

Biomedical Reports, Год журнала: 2023, Номер 20(2)

Опубликована: Дек. 19, 2023

Glioblastoma (GB) is one of the most adverse diagnoses in oncology. Complex current treatment results a median survival 15 months. Resistance to associated with presence cancer stem cells (CSCs). The present review aimed analyze mechanisms CSC plasticity, showing particular role β‑catenin regulating vital functions CSCs, and describe molecular Wnt‑independent increase levels, which influenced by local microenvironment CSCs. also analyzed reasons for low effectiveness using medication regulation proposed development immunotherapy scenarios tumor cell vaccines, containing heterogenous able producing multidirectional antineoplastic immune response. Additionally, possibility managing lymphopenia transplanting hematopoietic from healthy sibling clofazimine or other repurposed drugs that reduce concentration CSCs was discussed study.

Язык: Английский

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Harnessing the role of aberrant cell signaling pathways in glioblastoma multiforme: a prospect towards the targeted therapy

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Окт. 19, 2024

Язык: Английский

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Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma IDH Wildtype

Cancers, Год журнала: 2022, Номер 14(21), С. 5227 - 5227

Опубликована: Окт. 25, 2022

Serine/Threonine protein phosphatase 2A (PP2A) is a heterotrimeric (or occasionally, heterodimeric) with pleiotropic functions and ubiquitous expression. Despite the fact that they all contribute to dephosphorylation, multiple PP2A complexes exist which differ considerably by their subcellular localization substrate specificity, suggesting diverse functions. complex formation tightly regulated means of gene expression regulation transcription factors, microRNAs, post-translational modifications. Furthermore, constant competition between regulatory subunits taking place dynamically depending on spatiotemporal circumstance; many integral can outcompete rest, subjecting them proteolysis. modulation especially important in context brain tumors due its ability modulate distinct glioma-promoting signal transduction pathways, such as PI3K/Akt, Wnt, Ras, NF-κb, etc. also implicated DNA repair survival pathways are activated upon treatment glioma cells chemo-radiation. Depending cancer cell type, preclinical studies have shown some promise utilising activator or inhibitors overcome therapy resistance. This review has special focus “glioblastoma, IDH wild-type” (GBM) tumors, for options limited efficacy, tumor relapse inevitable.

Язык: Английский

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Ruxolitinib enhances cytotoxic and apoptotic effects of temozolomide on glioblastoma cells by regulating WNT signaling pathway-related genes

Medical Oncology, Год журнала: 2022, Номер 40(1)

Опубликована: Дек. 2, 2022

Язык: Английский

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Glioblastoma Biology, Genetics and Possible Therapies

Cells, Год журнала: 2023, Номер 12(16), С. 2063 - 2063

Опубликована: Авг. 14, 2023

Glioblastoma is the most aggressive intracranial tumor [...].

Язык: Английский

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Drug resistance in glioblastoma: from chemo- to immunotherapy

Cancer Drug Resistance, Год журнала: 2023, Номер 6(4), С. 688 - 708

Опубликована: Окт. 11, 2023

As the most common and aggressive type of primary brain tumor in adults, glioblastoma is estimated to end over 10,000 lives each year United States alone. Stand treatment for glioblastoma, including surgery followed by radiotherapy chemotherapy (i.e., Temozolomide), has been largely unchanged since early 2000. Cancer immunotherapy significantly shifted paradigm cancer management past decade with various degrees success treating many hematopoietic cancers some solid tumors, such as melanoma non-small cell lung (NSCLC). However, little progress made field neuro-oncology, especially application treatment. In this review, we attempted summarize drug resistance mechanisms from Temozolomide immunotherapy. Our intent not repeat well-known difficulty area blood-brain barrier, but provide fresh insights into molecular responsible summarizing recent literature. Through also hope share new ideas improving outcome

Язык: Английский

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Computational modeling and synthesis of pyridine variants of benzoyl-phenoxy-acetamide with high glioblastoma cytotoxicity and brain tumor penetration

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 28, 2023

Glioblastomas are highly aggressive brain tumors for which therapeutic options very limited. In a quest new anti-glioblastoma drugs, we focused on specific structural modifications to the benzoyl-phenoxy-acetamide (BPA) structure present in common lipid-lowering drug, fenofibrate, and our first prototype glioblastoma PP1. Here, propose extensive computational analyses improve selection of most effective drug candidates. Initially, over 100 BPA variations were analyzed their physicochemical properties, such as water solubility (- logS), calculated partition coefficient (ClogP), probability BBB crossing (BBB_SCORE), CNS penetration (CNS-MPO) cardiotoxicity (hERG), evaluated. This integrated approach allowed us select pyridine variants that show improved penetration, solubility, low cardiotoxicity. Herein top 24 compounds synthesized cell culture. Six them demonstrated toxicity with IC50 ranging from 0.59 3.24 µM. Importantly, one compounds, HR68, accumulated tumor tissue at 3.7 ± 0.5 µM, exceeds its (1.17 µM) by threefold.

Язык: Английский

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