A contemporary update on glioblastoma: molecular biology, current management, and a vision towards bio-adaptable personalized care

Habib, Ahmed; Pease, Matthew; Kodavali, Chowdari; Amankulor, Nduka; Zinn, Pascal O.

doi:10.1007/s11060-020-03671-w

Cited by 13 publications

(13 citation statements)

References 59 publications

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“…Heterogeneity is a widely known feature of GBM, as implied by its name: ’multiforme’. Numerous subclones develop in the early stage due to rapid mitoses [ 6 ]. As the process continues, determining the actual genomic status is barely possible.…”

Section: The Role Of Tumor Heterogeneity In Treatment Ineffectivenessmentioning

confidence: 99%

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

Hutóczki

Virga

Birkó

et al. 2021

IJMS

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Although treatment outcomes of glioblastoma, the most malignant central nervous system (CNS) tumor, has improved in the past decades, it is still incurable, and survival has only slightly improved. Advances in molecular biology and genetics have completely transformed our understanding of glioblastoma. Multiple classifications and different diagnostic methods were made according to novel molecular markers. Discovering tumor heterogeneity only partially explains the ineffectiveness of current anti-proliferative therapies. Dynamic heterogeneity secures resistance to combined oncotherapy. As tumor growth proceeds, new therapy-resistant sub clones emerge. Liquid biopsy is a new and promising diagnostic tool that can step up with the dynamic genetic change. Getting a ’real-time’ picture of a specific tumor, anti-invasion and multi-target treatment can be designed. During invasion to the peri-tumoral brain tissue, glioma cells interact with the extracellular matrix components. The expressional levels of these matrix molecules give a characteristic pattern, the invasion spectrum, which possess vast diagnostical, predictive and prognostic information. It is a huge leap forward combating tumor heterogeneity and searching for novel therapies. Using the invasion spectrum of a tumor sample is a novel tool to distinguish between histological subtypes, specifying the tumor grades or different prognostic groups. Moreover, new therapeutic methods and their combinations are under trial. These are crucial steps towards personalized oncotherapy.

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Section: The Role Of Tumor Heterogeneity In Treatment Ineffectivenessmentioning

confidence: 99%

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

Hutóczki

Virga

Birkó

et al. 2021

IJMS

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“…Despite being one of the most developed clinical fields, oncology still meets challenges related to certain malignancies which are aggressive, resistant to therapeutics and have poor prognosis. Glioblastoma belongs to this category of hard-to-treat tumors [ 1 , 2 ] and nowadays these properties are supposed to be related to a very specific cell type—glioblastoma stem cells (GSCs), a subpopulation of tumor cells capable of self-sustaining and associated with tumor formation, progression and recurrence [ 3 , 4 , 5 , 6 , 7 ]. It is also currently suggested that tumor stem cells may play a key role in the development of glioblastoma resistance to chemotherapy [ 5 , 6 , 7 , 8 , 9 , 10 ]; different model tumor lines may have different sensitivity to drugs [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dendrimer-microRNA Nanoformulations against Glioblastoma Stem Cells

et al. 2023

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Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Anti-tumor stem cell therapy calls for a new means of treatment. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation.

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“…The most common and aggressive form is GBM, which has a mean overall survival (OS) of 14.6 months and a 2-year survival rate of 26.5% with standard therapy [ 2 ]. The “integrated” [ 3 ] phenotypic and genotypic parameters for the central nervous system (CNS) tumor classification were introduced in the 2016 World Health Organization Classification of Tumors of the Central Nervous System [ 4 ], which emphasized the molecular impact on tumorigenesis and prognosis of glioma. The clinical characteristics of GBM that contribute to its dismal prognosis are aggressive growth, limited response to therapy, and inexorable recurrence [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Expression Profiles of HOXC6 Predict the Survival of Glioblastoma Patients and Correlate with Cell Cycle

Zhou

et al. 2022

Journal of Oncology

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The goal of this study was to investigate the homeobox (HOX) gene expression status and its prognostic value in glioblastoma multiforme (GBM) and to uncover the biological processes related to its expression. The prognostic value of HOX genes in GBM was systematically investigated by a genome-wide analysis of HOX gene expression profiles in GBM patient samples in The Cancer Genome Atlas (TCGA) project (microarray dataset) and validation datasets. Using the differentially expressed gene (DEG) analysis and a Cox regression model, we discovered that the HOXC6 could stratify patients into significantly different survival ( p = 0.0012 , log-rank test) groups in the training cohort. TCGA RNA-seq and GSE16011 datasets were used for validation. Multivariate Cox and stratification analysis indicated that HOXC6 was an independent prognostic factor after adjusting for other clinical covariates. Bioinformatic analysis suggested that the HOXC6 might be involved in the cell cycle-related biological processes and pathways that are well established in the context of glioblastoma tumorigenesis. We further explored the bioinformatic implications by gene set enrichment analysis (GSEA). Tumor cell biology experiments verified the role of HOXC6 in proliferation and cell cycle progression. In conclusion, HOXC6 might be a candidate biomarker gene for individual treatment optimization of glioblastoma. HOXC6 expression has a significant prognostic value and is related to the cell cycle process in glioblastoma.

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A contemporary update on glioblastoma: molecular biology, current management, and a vision towards bio-adaptable personalized care

Cited by 13 publications

References 59 publications

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

Effects of Dendrimer-microRNA Nanoformulations against Glioblastoma Stem Cells

Expression Profiles of HOXC6 Predict the Survival of Glioblastoma Patients and Correlate with Cell Cycle

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