Glioblastoma Therapy: Past, Present and Future

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2529 - 2529

Published: Feb. 21, 2024

Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians researchers, no significant improvement in survival has achieved since Stupp protocol became standard care (SOC) 2005. Despite multimodality treatments, recurrence is almost universal with rates under 2 years after diagnosis. Here, we discuss recent progress our understanding GB pathophysiology, particular, importance glioma stem cells (GSCs), tumor microenvironment conditions, epigenetic mechanisms involved growth, aggressiveness recurrence. The discussion on therapeutic strategies first covers SOC treatment targeted therapies that shown to interfere different signaling pathways (pRB/CDK4/RB1/P16

Language: Английский

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Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies

Acta Neurochirurgica, Journal Year: 2024, Volume and Issue: 166(1)

Published: April 2, 2024

Abstract Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over last decades, prognosis remains poor. Treatment of patients with glioblastoma a considerable challenge due to infiltrative nature tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists maximally safe microsurgical resection followed by adjuvant radio- chemotherapy temozolomide. In recent years, local therapies have been extensively investigated experimental as well translational levels. External stimuli-responsive such Photodynamic Therapy (PDT), Sonodynamic (SDT) Radiodynamic (RDT) can induce cell death mechanisms via generation reactive oxygen species (ROS) after administration five-aminolevulinic acid (5-ALA), which induces formation sensitizing porphyrins within tissue. Preliminary data from clinical trials are available. The aim this review summarize status therapeutic approaches an adjunct current standard glioblastoma.

Language: Английский

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Deciphering the hydrodynamics of lipid-coated microbubble sonoluminescence for sonodynamic therapy

Ultrasonics Sonochemistry, Journal Year: 2024, Volume and Issue: 111, P. 107090 - 107090

Published: Oct. 2, 2024

Sonodynamic therapy (SDT) is a minimally invasive targeted cancer that uses focused low-intensity ultrasound (<10 MPa, <10 W/cm

Language: Английский

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The Immunomodulatory Effects of Fluorescein-Mediated Sonodynamic Treatment Lead to Systemic and Intratumoral Depletion of Myeloid-Derived Suppressor Cells in a Preclinical Malignant Glioma Model

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 792 - 792

Published: Feb. 15, 2024

Fluorescein-mediated sonodynamic therapy (FL-SDT) is an extremely promising approach for glioma treatment, resulting from the combination of low-intensity focused ultrasound (FUS) with a sonosensitizer. In present study, we evaluated efficacy and immunomodulation SDT fluorescein as sonosensitizer in immunocompetent GL261 mice first time. vitro studies demonstrated that exposure cells to FL-SDT induced immunogenic cell death relevant upregulation MHC class I, CD80 CD86 expression. vivo were then performed treat glioma-bearing FL-SDT, alone, or FUS alone. Perturbation glioma-associated macrophage subset within immune microenvironment was by all treatments. Notably, depletion myeloid-derived suppressor (MDSCs) concomitant robust infiltration CD8+ T observed SDT-FL-treated mice, significant radiological delay progression consequent improvement survival. Tumor control improved survival also treated FL alone (median 41.5 days, p > 0.0001 compared untreated mice), reflecting considerable modulation microenvironment. Interestingly, high circulating lymphocyte-to-monocyte ratio very low proportion MDSCs predictive better FL- FL-SDT-treated than FUS-treated which elevated monocyte MDSC frequencies correlated worse The immunostimulatory potential treatment profound most immunosuppressive components encouraged exploration immunotherapeutic strategies.

Language: Английский

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Therapeutically targeting the unique disease landscape of pediatric high-grade gliomas

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 8, 2024

Pediatric high-grade gliomas (pHGG) are a rare yet devastating malignancy of the central nervous system’s glial support cells, affecting children, adolescents, and young adults. Tumors system account for leading cause pediatric mortality which present significantly grim prognosis. While past few decades have seen many cancers experiencing significant improvements in overall survival, prospect survival patients diagnosed with pHGGs has conversely remained unchanged. This can be attributed part to tumor heterogeneity existence blood-brain barrier. Advances discovery research substantiated unique subgroups displaying alternate responses different therapeutics varying degrees survival. highlights necessity approach clinical management disease an alternative subtype-dependent manner. review covers traditional approaches therapeutic pHGGs, limitations such methods emerging alternatives. Novel mutations predominate pHGG landscape highlighted potential targeting them subtype specific manner discussed. Collectively, this provides insight into issues need transformative progress arise during pHGGs.

Language: Английский

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Microbubble-Enhanced Focused Ultrasound for Infiltrating Gliomas

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1230 - 1230

Published: June 1, 2024

Infiltrating gliomas are challenging to treat, as the blood-brain barrier significantly impedes success of therapeutic interventions. While some clinical trials for high-grade have shown promise, patient outcomes remain poor. Microbubble-enhanced focused ultrasound (MB-FUS) is a rapidly evolving technology with demonstrated safety and efficacy in opening across various disease models, including infiltrating gliomas. Initially recognized its role augmenting drug delivery, potential MB-FUS augment liquid biopsy immunotherapy gaining research momentum. In this review, we will highlight recent advancements preclinical studies that utilize treat discuss future uses image-guided precision therapy using ultrasound.

Language: Английский

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H3K27-Altered Diffuse Midline Glioma of the Brainstem: From Molecular Mechanisms to Targeted Interventions

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1122 - 1122

Published: June 28, 2024

Pediatric high-grade gliomas are a devastating subset of brain tumors, characterized by their aggressive pathophysiology and limited treatment options. Among them, H3 K27-altered diffuse midline (DMG) the brainstem stand out due to distinct molecular features dismal prognosis. Recent advances in profiling techniques have unveiled critical role K27 alterations, particularly lysine-to-methionine mutation on position 27 (K27M) histone tail, pathogenesis DMG. These mutations result epigenetic dysregulation, which leads altered chromatin structure gene expression patterns DMG tumor cells, ultimately contributing phenotype The exploration targeted therapeutic avenues for has gained momentum recent years. Therapies, including modifiers, kinase inhibitors, immunotherapies, under active investigation; these approaches aim disrupt aberrant signaling cascades overcome various mechanisms resistance Challenges, blood-brain barrier penetration heterogeneity, require innovative improve drug delivery personalized strategies. This review aims provide comprehensive overview evolving understanding DMG, focusing intricate driving tumorigenesis/tumor progression current landscape emerging interventions.

Language: Английский

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Hierarchically Engineered Self-Adaptive Nanoplatform Guided Intuitive and Precision Interventions for Deep-Seated Glioblastoma

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Glioblastoma multiforme (GBM), particularly the deep-seated tumor where surgical removal is not feasible, poses great challenges for clinical treatments due to complicated biological barriers and risk of damaging healthy brain tissue. Here, we hierarchically engineer a self-adaptive nanoplatform (SAN) that overcomes delivery by dynamically adjusting its structure, surface charge, particle size, targeting moieties precisely distinguish between parenchyma cells. We further devise

Language: Английский

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Ultrasound binary microbubble drug delivery and drug synthesis for cancer treatment

Journal of Analytical Science & Technology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 8, 2025

Abstract Conventional chemotherapy is often constrained by the toxic effects of anticancer drugs, particularly in drug-resistant tumours requiring high doses for efficacy. This challenge underscores need innovative strategies to deliver medications effectively while minimizing systemic toxicity. Ultrasound-assisted drug delivery has emerged as a promising approach, enhancing localized concentrations, thereby improving treatment outcomes and reducing side effects. principles recent advancements ultrasound-assisted are highlighted. The article also describes strategy involving use ultrasound-responsive carriers (URCs) vivo synthesis. These URCs can transport two precursors (prodrugs). Targeted ultrasound exposure triggers release prodrugs, leading local synthesis "parent drug” that cytotoxic malignant cells. In addition, HIFU (high-intensity focused ultrasound) magnetic nanoparticles binary discussed detail. method could minimize harm healthy tissues organs, significantly efficacy toxicity targeted outcomes.

Language: Английский

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Focused ultrasound as a treatment modality for gliomas

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: May 15, 2024

Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax, etc.) at the bedside. Over past decade, advancements in technology have led to use of ultrasound treating many neurological conditions, such essential tremor and Parkinson’s disease, with high specificity. The convergence specific region interest/target while avoiding surrounding tissue has coined term “focused (FUS).” In tumor research, was an intraoperative guidance for resection. However, recent years, there been growing interest utilizing FUS therapeutic management brain tumors gliomas. This mini-review highlights current knowledge using treatment modality Furthermore, we discuss utility enhanced drug delivery central nervous system (CNS) highlight promising clinical trials utilize

Language: Английский

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