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Current Treatment Options in Oncology Jul 2020Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a... (Review)
Review
Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a novel, locoregional, antineoplastic treatment modality with favorable efficacy and safety being demonstrated in the most aggressive type of malignant gliomas, glioblastoma (GBM). In 2 large randomized, controlled phase 3 trials, the addition of TTFields was associated with increased overall survival when combined with adjuvant temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM (ndGBM) and comparable overall survival compared with standard chemotherapy in patients with recurrent GBM (rGBM). TTFields target cancer cells by several mechanisms of action (MoA) including suppression of proliferation, migration and invasion, disruption of DNA repair and angiogenesis, antimitotic effects, and induction of apoptosis and immunogenic cell death. Having several MoAs makes TTFields an attractive modality to combine with standard, salvage, and novel treatment regimens (e.g., radiotherapy, chemotherapy, and immunotherapy). Treatment within the field of malignant gliomas is evolving to emphasize combinatorial approaches that work synergistically to improve patient outcomes. Here, we review the current use of TTFields in GBM, discuss MOA and treatment delivery, and consider the potential for its wider adoption in other gliomas.
Topics: Algorithms; Brain Neoplasms; Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Factor Analysis, Statistical; Glioblastoma; Glioma; Humans; Radiofrequency Ablation; Treatment Outcome
PubMed: 32734509
DOI: 10.1007/s11864-020-00773-5 -
Nature Reviews. Clinical Oncology Jul 2017Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These... (Review)
Review
Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.
Topics: Central Nervous System Neoplasms; Glioma; Humans; Molecular Biology; Practice Guidelines as Topic; World Health Organization
PubMed: 28031556
DOI: 10.1038/nrclinonc.2016.204 -
Nature Aug 2019Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of... (Comparative Study)
Comparative Study
Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.
Topics: Animals; Cerebellar Neoplasms; Cerebellum; Child; Evolution, Molecular; Female; Fetus; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Glioma; Humans; Medulloblastoma; Mice; Sequence Analysis, RNA; Single-Cell Analysis; Time Factors; Transcription, Genetic; Transcriptome
PubMed: 31043743
DOI: 10.1038/s41586-019-1158-7 -
Theranostics 2022Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) involved in the regulation of the immune system and displayed a cell-type-specific pattern in...
Machine learning-based identification of tumor-infiltrating immune cell-associated lncRNAs for improving outcomes and immunotherapy responses in patients with low-grade glioma.
Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) involved in the regulation of the immune system and displayed a cell-type-specific pattern in immune cell subsets. Given the vital role of tumor-infiltrating lymphocytes in effective immunotherapy, we explored the tumor-infiltrating immune cell-associated lncRNA (TIIClncRNA) in low-grade glioma (LGG), which has never been uncovered yet. This study utilized a novel computational framework and 10 machine learning algorithms (101 combinations) to screen out TIIClncRNAs by integratively analyzing the sequencing data of purified immune cells, LGG cell lines, and bulk LGG tissues. The established TIIClnc signature based on the 16 most potent TIIClncRNAs could predict outcomes in public datasets and the Xiangya in-house dataset with decent efficiency and showed better performance when compared with 95 published signatures. The TIIClnc signature was strongly correlated to immune characteristics, including microsatellite instability, tumor mutation burden, and interferon γ, and exhibited a more active immunologic process. Furthermore, the TIIClnc signature predicted superior immunotherapy response in multiple datasets across cancer types. Notably, the positive correlation between the TIIClnc signature and CD8, PD-1, and PD-L1 was verified in the Xiangya in-house dataset. The TIIClnc signature enabled a more precise selection of the LGG population who were potential beneficiaries of immunotherapy.
Topics: Glioma; Humans; Immunologic Factors; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Machine Learning; RNA, Long Noncoding
PubMed: 35966587
DOI: 10.7150/thno.74281 -
Magnetic Resonance in Medical Sciences... Mar 2022One of the major issues in the surgical treatment of gliomas is the concern about maximizing the extent of resection while minimizing neurological impairment. Thus,... (Review)
Review
One of the major issues in the surgical treatment of gliomas is the concern about maximizing the extent of resection while minimizing neurological impairment. Thus, surgical planning by carefully observing the relationship between the glioma infiltration area and eloquent area of the connecting fibers is crucial. Neurosurgeons usually detect an eloquent area by functional MRI and identify a connecting fiber by diffusion tensor imaging. However, during surgery, the accuracy of neuronavigation can be decreased due to brain shift, but the positional information may be updated by intraoperative MRI and the next steps can be planned accordingly. In addition, various intraoperative modalities may be used to guide surgery, including neurophysiological monitoring that provides real-time information (e.g., awake surgery, motor-evoked potentials, and sensory evoked potential); photodynamic diagnosis, which can identify high-grade glioma cells; and other imaging techniques that provide anatomical information during the surgery. In this review, we present the historical and current context of the intraoperative MRI and some related approaches for an audience active in the technical, clinical, and research areas of radiology, as well as mention important aspects regarding safety and types of devices.
Topics: Brain Neoplasms; Diffusion Tensor Imaging; Glioma; Humans; Magnetic Resonance Imaging; Wakefulness
PubMed: 34880193
DOI: 10.2463/mrms.rev.2021-0116 -
Journal of Neuro-oncology Aug 2022Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or... (Review)
Review
PURPOSE
Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may experience no tumor-related symptoms and be incidentally diagnosed. These incidental low-grade gliomas (iLGG) maintain controversial treatment course despite scientific advancements. Here we highlight the recent advancements in classification, neuroimaging, and surgical management of these tumors.
METHODS
A review of the literature was performed. The authors created five subtopics of focus: histological criteria, diagnostic imaging, surgical advancements, correlation of surgical resection and survival outcomes, and clinical implications.
CONCLUSIONS
Alternating studies suggest that these tumors may experience higher mutational rates than their counterparts. Significant progress in management of gliomas, regardless of the grade, has been made through modern neurosurgical treatment modalities, diagnostic neuroimaging, and a better understanding of the genetic composition of these tumors. An optimal treatment approach for patients with newly diagnosed iLGG remains ill-defined despite multiple studies arguing in favor of safe maximal resection. Our review emphasizes the not so benign nature of incidental low grade glioma and further supports the need for future studies to evaluate survival outcomes following surgical resection.
Topics: Brain Neoplasms; Glioma; Humans; Neurosurgical Procedures; Treatment Outcome
PubMed: 35704158
DOI: 10.1007/s11060-022-04045-0 -
CNS Neuroscience & Therapeutics Aug 2023Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative... (Review)
Review
Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative combined chemo- and radio-therapy, are ineffective in improving patients' long-term survival. The tumor microenvironment (TME) consists of stromal cells, tumor components, and innate and acquired immune cells, and these cells, along with the extracellular matrix, regulate and communicate intercellularly to promote TME formation. The immune microenvironment plays a vital role in the development of glioma. Exosomes, which are extracellular vesicles (EVs), facilitate intercellular communication and regulation within the TME. Tumor cells can release exosomes to transmit messages, induce macrophage polarization, and inhibit immune cell activity, ultimately promoting metastasis and immune evasion. Moreover, immune cells can regulate tumorigenesis and progression through exosomes. This review summarized the biological properties of exosomes and their effects on the tumor microenvironment and provides an overview of the interactions between glioma cells and immune cells.
Topics: Humans; Exosomes; Tumor Microenvironment; Glioma; Extracellular Vesicles; Cell Communication; Neoplasms
PubMed: 37170647
DOI: 10.1111/cns.14239 -
Neurology India 2020Are we witnessing the end of the biopsy as we know it? Is this the start of a revolution in cancer diagnostics and treatment where analysis of somatic mutations present... (Review)
Review
BACKGROUND
Are we witnessing the end of the biopsy as we know it? Is this the start of a revolution in cancer diagnostics and treatment where analysis of somatic mutations present in the blood, CSF, or urine followed by targeted therapy replaces the traditional surgery followed by chemo-radiation? Since 2016, molecular markers are an integral part of the 'glioma' treatment decision-making process- diagnostic, prognostic, and therapeutic. A lot of these somatic mutations that identify and prognosticate tumors are also detected in the adjoining bio-fluids in serum or CSF- the sampling of which is known as liquid biopsy.
OBJECTIVE
The objective of this study is to review the advancement of scientific techniques that now allows the investigation of these bio-fluids, to diagnose, prognosticate and treat gliomas.
MATERIAL AND METHODS
This review article is an exhaustive review of the literature that summarises the role of the three main liquid biopsy modalities- Circulating Tumor Cells, Cell-free Tumor DNA and Exosomes in the detection of known diagnostic and prognostic markers in gliomas.
RESULTS
The current review highlights the strengths and weaknesses of the diffrerent modalities in use, and their potential use in the clinical setting.
CONCLUSION
Liquid biopsies hold tremendous potential in the diagnosis and management of gliomas in the future.
Topics: Biomarkers, Tumor; Glioma; Humans; Liquid Biopsy; Neoplastic Cells, Circulating; Prognosis
PubMed: 33342856
DOI: 10.4103/0028-3886.304105 -
Frontiers in Immunology 2023Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory...
INTRODUCTION
Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.
METHODS
In the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.
RESULTS
TMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.
DISCUSSION
Taken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.
Topics: Humans; Astrocytoma; Epithelial-Mesenchymal Transition; Glioma; Prognosis; Transcriptome
PubMed: 37261362
DOI: 10.3389/fimmu.2023.1173518 -
CNS Oncology Jan 2018High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases,... (Review)
Review
High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.
Topics: Brain Neoplasms; Disease Management; Glioma; Humans; Neoplasm Grading
PubMed: 29241354
DOI: 10.2217/cns-2017-0026