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

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 2975 - 2975

Published: Aug. 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.

Language: Английский

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Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7743 - 7743

Published: July 15, 2024

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food Drug Administration (FDA). Significant barriers to effectiveness of include cytokine release syndrome (CRS), neurotoxicity in case Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), escape, modest antitumor activity, restricted trafficking, limited persistence, immunosuppressive microenvironment, senescence exhaustion CAR-Ts. Furthermore, cancer drug resistance remains major problem clinical practice. therapy, combination with checkpoint blockades bispecific engagers (BiTEs) other drugs, appears be an appealing strategy. Many these agents shown impressive results, combining efficacy tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) miRNAs may play important role toxicity, relapse assessment, prediction, can implicated applications establishing safe efficacious personalized medicine. However, further research required fully comprehend particular side effects immunomodulation, ascertain best order this medication conventional chemotherapy targeted therapies, find reliable predictive biomarkers.

Language: Английский

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Nanosystems at Nexus: Navigating Nose-to-Brain Delivery for Glioblastoma Treatment

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Glioblastoma multiforme (GBM) is considered to be one of the most devastating brain tumors with a shorter life expectancy. Several factors contribute dismal prognosis GBM patients including complicated nature GBM, ability tumor cells resist treatment, and difficulty delivering drugs because barriers like blood-brain barrier (BBB) blood-tumor (BTB). The unique challenges posed by BBB in therapeutic agents have led development innovative nanotechnology-based approaches. By exploiting olfactory/trigeminal pathway, nanosystems offer promising strategy for targeted drug delivery brain, glioblastoma particular. This review contemplates varied nanocarriers, polymeric nanoparticles, lipid-based nanosystems, situ gel formulations, peptide, stem cell-based nanoformulations, signifying their utility targeting minimal systemic side effects. Emerging trends gene therapy immunotherapy context treatment also been discussed. Since safety paramount aspect any product get approved, this delves into toxicological considerations associated intranasal nanosystems. Regulatory aspects critical successful products are explored review. Overall, underscores significant advancements nanotechnology nose-to-brain its potential impact on management.

Language: Английский

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Mechanistic insights into CDCA gene family-mediated glioblastoma progression: implications for diagnosis, prognosis, and therapeutic targeting

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 20, 2025

Abstract Background Glioblastoma (GBM) is a highly aggressive brain tumor characterized by poor prognosis and limited therapeutic options. Understanding the molecular mechanisms driving GBM progression essential for developing more effective diagnostic approaches. Specifically, investigating Cell Division Cycle-Associated (CDCA) genes offers new perspectives on cell cycle regulation proliferation of cells, which are key factors in growth resistance to treatment. These have not been extensively studied GBM, making them promising area targeted research potential interventions. This project was launched elucidate pathogenic, diagnostic, roles CDCA GBM. Methodology Total RNA extracted from lines followed RT-qPCR analyze expression genes. The validation, prognostic significance, mutational analysis were performed using various databases. Functional assays, including gene knockdown, colony formation, proliferation, wound healing, conducted U87MG cells assess role CDCA7 CDCA8 Results 12 6 normal revealed significant overexpression these ROC curve demonstrated excellent potential, with AUC values 1 most indicates that effectively distinguishes cells. Validation additional TCGA data confirmed upregulation tumors, association cancer-related pathways. Survival showed higher correlated patients. Mutation, CNV, methylation analyses alterations genes, further supporting their Additionally, linked immune modulation cycle-related functions, suggesting involvement evasion proliferation. Knockdown experiments reduction migration, highlighting as targets. Conclusion Overall, our findings suggest could serve both biomarkers targets

Language: Английский

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Engineered nanovesicles targeting SERPINE1 overcome temozolomide resistance in glioblastoma

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111763 - 111763

Published: March 1, 2025

Language: Английский

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Evaluation of Microvascular Density in Glioblastomas in Relation to p53 and Ki67 Immunoexpression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6810 - 6810

Published: June 20, 2024

Glioblastoma is the most aggressive tumor in central nervous system, with a survival rate of less than 15 months despite multimodal therapy. Tumor recurrence frequently occurs after removal. Tumoral angiogenesis, formation neovessels, has positive impact on progression and invasion, although there are controversial results specialized literature regarding its survival. This study aims to correlate immunoexpression angiogenesis markers (CD34, CD105) proliferation index Ki67 p53 primary secondary glioblastomas. retrospective included 54 patients diagnosed glioblastoma at Pathology Department County Emergency Clinical Hospital Târgu Mureș. Microvascular density was determined using CD34 CD105 antibodies, were correlated p53, IDH1, ATRX Ki67. The number neoformed blood vessels varied among cases, characterized by different shapes calibers, endothelial cells showing modified morphology moderate marked pleomorphism. Neovessels glomeruloid aspect, associated intense positivity for or cells, observed, characteristic Mean microvascular values higher marker all though no statistically significant differences compared CD105. Mutant IDH1 glioblastomas, wild-type those above 20% showed more abundant density, statistical correlations not reaching significance. highlighted variety percentage intervals glioblastomas immunohistochemical CD105, respectively, correlation between evaluated

Language: Английский

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Enhanced Cytotoxic Effects of Cold Plasma Deposition of Topotecan: A Novel Approach for Local Cancer Drug Delivery to Glioblastoma Cells

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 201 - 201

Published: Jan. 9, 2025

Despite the numerous advances in glioblastoma multiforme (GBM) treatment, GBM remains as most malignant and aggressive form of brain cancer, characterized by a very poor outcome, highlighting ongoing need for development new therapeutic strategies. A novel intervention using plasma-assisted local delivery oncology drugs was developed to mediate drug delivery, which might improve uptake and/or chemotherapeutic action. Topotecan (TPT), water-soluble topoisomerase I inhibitor with major cytotoxic effects during S-phase cell cycle, selected candidate because despite its potent antitumor activity, systemic administration is limited due low crossing blood-brain barrier. For these reasons, TPT may be repurposed combined therapies. We aimed explore options treatment where systematic challenging, combination between plasma-based technologies on human cancer line (U-251mg). The evaluation direct plasma deposition helium jet (J-Plasma, Apyx Medical) nebulizer onto U-251mg cells grown 2D or 3D culture showed reduction metabolic activity mass decreased long-term survival, indicating synergistic treatment. approach confirmed temozolomide (TMZ) standard well two skin lines. These results revealed pathway combinations approaches application range cancers.

Language: Английский

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Joint analysis of single-cell RNA sequencing and bulk transcriptome reveals the heterogeneity of the urea cycle of astrocytes in glioblastoma

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106835 - 106835

Published: Feb. 1, 2025

Language: Английский

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Potential of Curcumin and Its Analogs in Glioblastoma Therapy

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 351 - 351

Published: March 18, 2025

Curcumin, a polyphenol found in turmeric, demonstrates multifaceted anti-cancer activity against glioblastoma. Its therapeutic potential stems from its ability to modulate various molecular pathways implicated glioblastoma development and progression, enhance the effectiveness of radiation therapy, induce cancer cell death through diverse mechanisms, including apoptosis, autophagy, cycle arrest. These combined actions make curcumin promising candidate for treatment, warranting further investigation into clinical application. In this review, we summarize latest research on analogs' therapy.

Language: Английский

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Exploring Multi-Target Therapeutic Strategies for Glioblastoma via Endogenous Network Modeling

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3283 - 3283

Published: April 1, 2025

Medical treatment of glioblastoma presents a significant challenge. A conventional medication has limited effectiveness, and single-target therapy is usually effective only in the early stage treatment. Recently, there been increasing focus on multi-target therapies, but vast range possible combinations makes clinical experimentation implementation difficult. From perspective systems biology, this study conducted simulations for based dynamic analysis previously established endogenous networks, validated with single-cell RNA sequencing data. Several potentially target were identified. The findings also highlight necessity rather than intervention strategies cancer treatment, as well promise applications personalized therapies.

Language: Английский

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