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The multifaceted mechanisms of malignant glioblastoma progression and clinical implications.

ABSTRACT: With the application of high throughput sequencing technologies at single-cell resolution, studies of the tumor microenvironment in glioblastoma, one of the most aggressive and invasive of all cancers, have revealed immense cellular and tissue heterogeneity. A unique extracellular scaffold system adapts to and supports progressive infiltration and migration of tumor cells, which is characterized by altered composition, effector delivery, and mechanical properties. The spatiotemporal interactions between malignant and immune cells generate an immunosuppressive microenvironment, contributing to the failure of effective anti-tumor immune attack. Among the heterogeneous tumor cell subpopulations of glioblastoma, glioma stem cells (GSCs), which exhibit tumorigenic properties and strong invasive capacity, are critical for tumor growth and are believed to contribute to therapeutic resistance and tumor recurrence. Here we discuss the role of extracellular matrix and immune cell populations, major components of the tumor ecosystem in glioblastoma, as well as signaling pathways that regulate GSC maintenance and invasion. We also highlight emerging advances in therapeutic targeting of these components.

SUBMITTER: Sun R

PROVIDER: S-EPMC9758111 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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The multifaceted mechanisms of malignant glioblastoma progression and clinical implications.

Sun Rui R Kim Albert H AH

Cancer metastasis reviews 20220803 4

With the application of high throughput sequencing technologies at single-cell resolution, studies of the tumor microenvironment in glioblastoma, one of the most aggressive and invasive of all cancers, have revealed immense cellular and tissue heterogeneity. A unique extracellular scaffold system adapts to and supports progressive infiltration and migration of tumor cells, which is characterized by altered composition, effector delivery, and mechanical properties. The spatiotemporal interactions ...[more]

PMID: 35920986

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Project description:BackgroundThis study was designed to explore the progression patterns of IDH-wildtype glioblastoma (GBM) at first recurrence after chemoradiotherapy.MethodsRecords from 247 patients who underwent progression after diagnosis of IDH-wildtype GBM was retrospectively reviewed. Progression patterns were classified as either local, distant, subependymal or leptomeningeal dissemination based on the preoperative and serial postoperative radiographic images. The clinical and molecular characteristics of different progression patterns were analyzed.ResultsA total of 186 (75.3%) patients had local progression, 15 (6.1%) patients had distant progression, 33 (13.3%) patients had subependymal dissemination, and 13 (5.3%) patients had leptomeningeal dissemination. The most favorable survival occurred in patients with local progression, while no significant difference of survival was found among patients with distant progression, subependymal or leptomeningeal dissemination who were thereby reclassified into non-local group. Multivariable analysis showed that chemotherapy was a protective factor for non-local progression, while gender of male, subventricular zone (SVZ) involvement and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation were confirmed as risk factors for non-local progression (P < 0.05). Based on the factors screened by multivariable analysis, a nomogram was constructed which conferred high accuracy in predicting non-local progression. Patients in non-local group could be divided into long- and short-term survivors who differed in the rates of SVZ involvement, MGMT promoter methylation and reirradiation (P < 0.05), and a nomogram integrating these factors showed high accuracy in predicting long-term survivors.ConclusionPatients harboring different progression patterns conferred distinct clinical and molecular characteristics. Our nomograms could provide theoretical references for physicians to make more personalized and precise treatment decisions.

Dataset Information

The multifaceted mechanisms of malignant glioblastoma progression and clinical implications.

Publications

The multifaceted mechanisms of malignant glioblastoma progression and clinical implications.

Similar Datasets

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