Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches

Tripathy, Dev Kumar; Panda, Lakshmi Priya; Biswal, Suryanarayan; Barhwal, Kalpana

doi:10.3389/fphar.2024.1355242

Cited by 3 publications

References 191 publications

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3D Brain Vascular Niche Model Captures Invasive Behavior and Gene Signatures of Glioblastoma

Lee,

Tejero,

Silvia

et al. 2024

Preprint

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Glioblastoma (GBM) is a lethal brain cancer with no effective treatment; understanding how GBM cells respond to tumor microenvironment remains challenging as conventional cell cultures lack proper cytoarchitecture whilein vivoanimal models present complexity all at once. Developing a culture system to bridge the gap is thus crucial. Here, we employed a multicellular approach using human glia and vascular cells to optimize a 3-dimensional (3D) brain vascular niche model that enabled not only long-term culture of patient derived GBM cells but also recapitulation of key features of GBM heterogeneity, in particular invasion behavior and vascular association. Comparative transcriptomics of identical patient derived GBM cells in 3D andin vivoxenotransplants models revealed that glia-vascular contact induced genes concerning neural/glia development, synaptic regulation, as well as immune suppression. This gene signature displayed region specific enrichment in the leading edge and microvascular proliferation zones in human GBM and predicted poor prognosis. Gene variance analysis also uncovered histone demethylation and xylosyltransferase activity as main themes for gene adaption of GBM cellsin vivo. Furthermore, our 3D model also demonstrated the capacity to provide a quiescence and a protective niche against chemotherapy. In summary, an advanced 3D brain vascular model can bridge the gap between 2D cultures andin vivomodels in capturing key features of GBM heterogeneity and unveil previously unrecognized influence of glia-vascular contact for transcriptional adaption in GBM cells featuring neural/synaptic interaction and immunosuppression.

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3D Brain Vascular Niche Model Captures Invasive Behavior and Gene Signatures of Glioblastoma

Lee,

Tejero,

Silvia

et al. 2024

Preprint

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Glioma Stem Cells: GPRC5A as a Novel Predictive Biomarker and Therapeutic Target Associated with Mesenchymal and Stemness Features

Aghamiri,

Amin

2024

Applied Sciences

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Glioblastoma multiforme (GBM) represents the deadliest form of brain cancer, characterized by complex interactions within its microenvironment. Despite the understanding of GBM biology, GBM remains highly resistant to any therapy. Therefore, defining innovative biomarkers in GBM can provide insights into tumor biology and potential therapeutic targets. In this study, we explored the potential of GPRC5A to serve as a pertinent biomarker for GBM. We utilized the GBM-TCGA dataset and presented the reproducible bioinformatics analysis for our results. We identified that GPRC5A expression was significantly upregulated in GBM compared to normal tissues, with higher levels correlating with poor overall survival (OS) and progression-free interval (PFI). Moreover, it was associated with key genetic mutations, particularly NF1 and PTEN mutations, and strongly correlated with the mesenchymal stem-like phenotype. GPRC5A was also predominantly associated with aggressive GBM features, including hypoxia, high extracellular matrix (ECM) environments, and extensive stromal and immune infiltrations. Its strong correlation with mesenchymal markers and hypoxic regions underscores its potential as a biomarker and therapeutic target in GBM. These findings provide valuable insights into the role of GPRC5A in GBM pathology and its potential impact as a target for GBM stratifications and treatment strategies.

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

Rahman,

Ali

2024

Cancers

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

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Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches

Cited by 3 publications

References 191 publications

3D Brain Vascular Niche Model Captures Invasive Behavior and Gene Signatures of Glioblastoma

3D Brain Vascular Niche Model Captures Invasive Behavior and Gene Signatures of Glioblastoma

Glioma Stem Cells: GPRC5A as a Novel Predictive Biomarker and Therapeutic Target Associated with Mesenchymal and Stemness Features

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

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