Recent Treatment Strategies and Molecular Pathways in Resistance Mechanisms of Antiangiogenic Therapies in Glioblastoma

Cancers, Год журнала: 2024, Номер 16(17), С. 2975 - 2975

Опубликована: Авг. 27, 2024

Malignant gliomas present great difficulties in treatment, with little change over the past 30 years median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing formation new vasculature (antiangiogenic treatments) or destroying formed tumor (vascular disrupting agents) show promise. This study summarizes existing knowledge regarding processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses activation redundant proangiogenic pathways, heightened cell invasion metastasis, induced hypoxia, creation vascular mimicry channels, regulation immune microenvironment. Subsequently, we explore potential strategies overcome this resistance, such as combining other methods, personalizing treatments for each patient, focusing on therapeutic targets, incorporating immunotherapy, utilizing drug delivery systems based nanoparticles. Additionally, would like discuss limitations methods future directions enhance beneficial effects patients GBM. Therefore, review aims research outcome GBM provide a more promising opportunity thoroughly exploring mechanisms investigating novel strategies.

Язык: Английский

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Understanding Neovascularization in Glioblastoma: Insights from the Current Literature

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2763 - 2763

Опубликована: Март 19, 2025

Glioblastomas (GBMs), among the most aggressive and resilient brain tumors, characteristically exhibit high angiogenic potential, leading to formation of a dense yet aberrant vasculature, both morphologically functionally. With these premises, numerous expectations were initially placed on anti-angiogenic therapies, soon dashed by their limited efficacy in concretely improving patient outcomes. Neovascularization GBM emerged as complex, dynamic, heterogeneous process, hard manage with classical standard care. Growing evidence has revealed existence non-canonical strategies angiogenesis, variously exploited meet its ever-increasing metabolic demand differently involved tumor progression, recurrence, escape from treatments. In this review, we provide an accurate description each neovascularization mode encountered tumors date, highlighting molecular players signaling cascades primarily involved. We also detail key architectural functional aspects characteristic vascular compartment because intricate crosstalk between different networks. Additionally, explore repertoire emerging therapies against that are currently under study, concluding question: faced such challenging scenario, could combined tailored patient’s genetic signatures, represent effective game changer?

Язык: Английский

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Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition

Biomedicines, Год журнала: 2025, Номер 13(1), С. 133 - 133

Опубликована: Янв. 8, 2025

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy chemotherapy. Sesquiterpene triterpenoids (STLs) their semi-synthetic analogs are considered as a promising source novel anti-tumor agents due low systemic toxicity multi-target pharmacological effects on key processes associated with tumor progression. The current review aims systematize knowledge anti-glioblastoma potential STLs accumulated over last decade identify in glioblastoma cells that susceptible action STLs. An analysis published data clearly demonstrated STLs, which can successfully cross blood-brain barrier, exert complex inhibitory effect through induction "mitochondrial dysfunction-oxidative stress-apoptosis" axis, inhibition glucose metabolism cell cycle phase transition, suppression motility invasion blockade proneural-mesenchymal transition. Taken together, this highlights not only able induce death, but also effectively affect diffusive spread, suggests possible directions for further investigation context better understand mechanism action.

Язык: Английский

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Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance

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

Опубликована: Фев. 26, 2025

Glioblastoma (GBM) is one of the deadliest tumors due to its high aggressiveness and resistance standard therapies, resulting in a dismal prognosis. This lethal tumor carries out metabolic reprogramming order modulate specific pathways, providing metabolites that promote GBM cells proliferation limit efficacy treatments. Indeed, remodels glucose metabolism undergoes Warburg effect, fuelling glycolysis even when oxygen available. Moreover, recent evidence revealed rewiring nucleotide, lipid iron metabolism, not only an increased growth, but also radio- chemo-resistance. Thus, while on hand advantage for GBM, other it may represent exploitable target hamper progression. Lately, number studies focused drugs targeting uncover their effects therapy resistance, demonstrating some these are effective, combination with conventional treatments, sensitizing radiotherapy chemotherapy. However, heterogeneity could lead plethora alterations among subtypes, hence treatment might be effective proneural mesenchymal ones, which more aggressive resistant approaches. review explores key mechanisms involvement highlighting how acts as double-edged sword taking into account pathways seem offer promising options GBM.

Язык: Английский

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Advancing Glioblastoma Therapy: Learning From the Past and Innovations for the Future

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217601 - 217601

Опубликована: Март 1, 2025

Язык: Английский

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Machine learning and multi-omics analysis reveal key regulators of proneural–mesenchymal transition in glioblastoma

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Июнь 5, 2025

Glioblastoma (GBM) is classified into subtypes according to the molecular expression profile; proneural subtype has a relatively good prognosis, and mesenchymal type most aggressive form with worst prognosis. GBM undergoes proneural-mesenchymal transition (PMT) during its evolution or in response changes microenvironment therapeutic interventions. PMT accompanied by infiltration of non-tumor cells, decreased tumor purity, immune evasion. However, cellular mechanisms underlying remain unclear. Differentially expressed genes (DEGs) were identified using transcriptome datasets, prognostic analysis was performed screen for PMT-related (PMTRGs). Consensus cluster followed Gene Set Enrichment Analysis, Ontology, Kyoto Encyclopedia Genes Genomes analyses DEGs determine biological functions pathways regulated PMTRGs. CIBERSORT, TIMER, MCPCOUNTER, XCELL algorithms used analyze cell patterns. The TIDE algorithm examine immunotherapy scores. Lasso, Cox, Step machine learning construct optimal risk assessment model. PMTRG patterns patient tissues different subsets examined proteomics single-cell data analysis. Seventeen PMTRGs subtypes. PMTRG-related mRNA interactions protein-protein interaction networks associated activity GBM. based on divided three independent subclusters. Functional pathway showed that highly C1 subcluster, which isoforms, pathways, poor stronger responses. Four evaluation had high levels molecule model can effectively predict prognosis patients. Proteomic from immunohistochemistry suggested are predominantly monocytes, macrophages, blood vessels rather than cells. This study 17 key These mainly cells suggesting events arise activation derived bone marrow vessels. findings provide new evidence targets treatment

Язык: Английский

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New ALKBH2 and ALKBH5 inhibitors for treating glioblastoma

Results in Chemistry, Год журнала: 2024, Номер 9, С. 101645 - 101645

Опубликована: Июль 1, 2024

Glioblastoma is an aggressive brain tumor with high mortality and a median survival of about 15 months. Starting from our previous published compound, MV1035 that inhibited migration invasiveness glioblastoma U87 cells, also exhibited synergic effect in combination the alkylating agent Temozolomide, we identified new active molecules, aim to understand key motifs responsible for activity against DNA repair protein ALKBH2 RNA demethylase ALKBH5. We modified original structure MV1035, synthesizing molecules have been tested through MTT assay, cell-free assay ALKBH5 assay. found compound 6 able reduce both obtained important information these inhibitors. However, considering complexity, heterogeneity plasticity GBM GSC will need be validated vivo.

Язык: Английский

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Complement C1S is a potential prognostic biomarker and associated with M2 macrophage infiltration in gliomas: From bioinformatics to comprehensive experimental validation

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113573 - 113573

Опубликована: Ноя. 7, 2024

Язык: Английский

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SARS CoV-2 in tumor tissue in glioblastoma patients – preliminary study

Current Issues in Pharmacy and Medical Sciences, Год журнала: 2024, Номер 37(4), С. 216 - 220

Опубликована: Ноя. 28, 2024

Abstract SARS-CoV-2 infection often causes neurological disorders. Experimental studies on an animal model have shown that is able to cross the blood-brain barrier. Researchers also discovered can infect glial cells. Gliomas are most common type of brain tumor. Oncological patients at high risk infections, including SARS-CoV-2. Moreover, their weakened immunity level antibodies after or vaccination be lower than in healthy population. Therefore, aim our study was evaluate occurrence RNA tumor tissue collected during surgery. We tested anti-SARS-CoV-2 these patients. The obtained results indicate tropism virus – glioblastoma. anti-SARS higher with detected tumour tissue.

Язык: Английский

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Bullatine A suppresses glioma cell growth by targeting SIRT6

Heliyon, Год журнала: 2024, Номер 11(1), С. e41440 - e41440

Опубликована: Дек. 24, 2024

Gliomas are the most common primary tumors of nervous system, which is generally treated using adjuvant chemotherapy following surgical resection. However, patient survival time still short, and there currently no successful treatment for highly malignant gliomas. Bullatine A (BLA) a diterpenoid alkaloid genus Aconitum antirheumatic anti-inflammatory pharmacological properties. The effects BLA on gliomas have not yet been elucidated. In this study, we investigated human brain glioblastoma cells. Our results showed that inhibited proliferation U87MG U251 cells in dose-dependent manner decreased their rate. dose-dependently induced apoptosis cells, upregulated expression cleaved caspase-9, caspase-3 pro-apoptotic protein, Bax downregulated Bcl-2 anti-apoptotic protein. Moreover, cell cycle arrest G2/M phase, p-ERK Myc proteins. Further, significantly acetylation histones H3K9 H3K56, protein deacetylase SIRT6. Mechanistic studies revealed effect inducing inhibiting glioma was blocked by SIRT6 knockout. summary, our study indicated potential therapeutic agent targets to inhibit induce apoptosis.

Язык: Английский

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