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The New England Journal of Medicine Aug 2023
Topics: Humans; Brain Neoplasms; Glioma; Isocitrate Dehydrogenase; Mutation; Neoplasm Grading; Antineoplastic Agents; Molecular Targeted Therapy
PubMed: 37585633
DOI: 10.1056/NEJMe2305602 -
Nature Communications Sep 2023Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we...
Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.
Topics: Humans; Brain Neoplasms; Multiparametric Magnetic Resonance Imaging; Homozygote; Sequence Deletion; Glioma; Magnetic Resonance Imaging; Biological Products
PubMed: 37770427
DOI: 10.1038/s41467-023-41559-1 -
Nature Communications Jul 2023Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to...
Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate MAPKi-sensitive and non-sensitive cells in the GDSC dataset and significantly correlate with response to MAPKi in an independent PDX dataset. The MSSs discern gliomas with varying MAPK alterations and are higher in pLGG compared to other pediatric CNS tumors. Heterogenous MSSs within pLGGs with the same MAPK alteration identify proportions of potentially sensitive patients. The MEKi MSS predicts treatment response in a small set of pLGG patients treated with trametinib. High MSSs correlate with a higher immune cell infiltration, with high expression in the microglia compartment in single-cell RNA sequencing data, while low MSSs correlate with low immune infiltration and increased neuronal score. The MSSs represent predictive tools for the stratification of pLGG patients and should be prospectively validated in clinical trials. Our data supports a role for microglia in the response to MAPKi.
Topics: Child; Humans; Glioma; Cell Line; Protein Kinase Inhibitors; Biomarkers
PubMed: 37500667
DOI: 10.1038/s41467-023-40235-8 -
Cancer Cell Jan 2024Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1)...
Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations; and (3) streamlining clinical efforts including biopsy, CNS-drug delivery, endpoint determination, and response monitoring. We highlight the importance of comprehensive collaboration to advance the understanding, diagnostics, and therapeutics for DMGs.
Topics: Humans; Child; Brain Neoplasms; Glioma; Mutation; Brain; Biopsy
PubMed: 38039965
DOI: 10.1016/j.ccell.2023.11.002 -
Tumori Aug 2023The purpose of this editorial is to consider some of the aspects of the diagnosis and treatment of adult gliomas. These are rare diseases with all their limitations....
The purpose of this editorial is to consider some of the aspects of the diagnosis and treatment of adult gliomas. These are rare diseases with all their limitations. Innovations in diagnosis and therapy and their constraints are analyzed and compared with the current treatment reality. Aspects affecting these patients' quality of life are highlighted.
Topics: Humans; Adult; Brain Neoplasms; Quality of Life; Glioma
PubMed: 36964665
DOI: 10.1177/03008916231159716 -
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 -
Cancer Biology & Therapy Dec 2024Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous... (Review)
Review
Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.
Topics: Humans; Glioma; TRPM Cation Channels; Brain Neoplasms; Signal Transduction; Animals
PubMed: 38680092
DOI: 10.1080/15384047.2024.2338955 -
Journal of Integrative Neuroscience Aug 2023Although some progress has been made in tumor treatment, gliomas remain one of the tumors that can still seriously threaten human life and health. Due to the... (Review)
Review
Although some progress has been made in tumor treatment, gliomas remain one of the tumors that can still seriously threaten human life and health. Due to the particularity of the immune microenvironment of the central nervous system and the strong invasiveness of tumors, the treatment of gliomas remains a major challenge. Currently, researchers have explored a large number of immunotherapy programs to improve the survival and prognosis of glioma patients, including tumor vaccines, immune checkpoint inhibitors, adoptive cell transfer therapy, viral vector therapy, and genetic engineering therapy. The goal of these programs is to activate or change the immunosuppressive environment and target tumor cells through drugs, combined with surgical resection, radiotherapy, chemotherapy, and anti-angiogenesis drugs, to achieve the purpose of treating glioma. This review briefly describes the immunosuppressive microenvironment of gliomas and summarizes recent immunotherapeutic strategies and their progress. The aim is to summarize the latest immunotherapies for the treatment of gliomas and provide new research directions.
Topics: Humans; Immunotherapy; Glioma; Central Nervous System; Tumor Microenvironment
PubMed: 37735122
DOI: 10.31083/j.jin2205118 -
Clinical and Translational Medicine Oct 2023Aggressive brain tumours, whether primary gliomas or secondary metastases, are characterised by hypervascularisation and are fatal. Recent research has emphasised the... (Review)
Review
BACKGROUND
Aggressive brain tumours, whether primary gliomas or secondary metastases, are characterised by hypervascularisation and are fatal. Recent research has emphasised the crucial involvement of endothelial cells (ECs) in all brain tumour genesis and development events, with various patterns and underlying mechanisms identified.
MAIN BODY
Here, we highlight recent advances in knowledge about the contributions of ECs to brain tumour development, providing a comprehensive summary including descriptions of interactions between ECs and tumour cells, the heterogeneity of ECs and new models for research on ECs in brain malignancies. We also discuss prospects for EC targeting in novel therapeutic approaches.
CONCLUSION
Interventions targeting ECs, as an adjunct to other therapies (e.g. immunotherapies, molecular-targeted therapies), have shown promising clinical efficacy due to the high degree of vascularisation in brain tumours. Developing precise strategies to target tumour-associated vessels based on the heterogeneity of ECs is expected to improve anti-vascular efficacy.
Topics: Humans; Endothelial Cells; Brain Neoplasms; Neovascularization, Pathologic; Glioma
PubMed: 37830128
DOI: 10.1002/ctm2.1433 -
Pharmacological Reports : PR Apr 2024Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous system. While the treatment of other neoplasms is increasingly more efficacious the... (Review)
Review
Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous system. While the treatment of other neoplasms is increasingly more efficacious the median survival rate of GBM patients remains low and equals about 14 months. Due to this fact, there are intensive efforts to find drugs that would help combat GBM. Nowadays cannabinoids are becoming more and more important in the field of cancer and not only because of their properties of antiemetic drugs during chemotherapy. These compounds may have a direct cytotoxic effect on cancer cells. Studies indicate GBM has disturbances in the endocannabinoid system-changes in cannabinoid metabolism as well as in the cannabinoid receptor expression. The GBM cells show expression of cannabinoid receptors 1 and 2 (CB1R and CB2R), which mediate various actions of cannabinoids. Through these receptors, cannabinoids inhibit the proliferation and invasion of GBM cells, along with changing their morphology. Cannabinoids also induce an intrinsic pathway of apoptosis in the tumor. Hence the use of cannabinoids in the treatment of GBM may be beneficial to the patients. So far, studies focusing on using cannabinoids in GBM therapy are mainly preclinical and involve cell lines and mice. The results are promising and show cannabinoids inhibit GBM growth. Several clinical studies are also being carried out. The preliminary results show good tolerance of cannabinoids and prolonged survival after administration of these drugs. In this review, we describe the impact of cannabinoids on GBM and glioma cells in vitro and in animal studies. We also provide overview of clinical trials on using cannabinoids in the treatment of GBM.
Topics: Humans; Mice; Animals; Cannabinoids; Glioblastoma; Glioma; Endocannabinoids; Antineoplastic Agents; Brain Neoplasms
PubMed: 38457018
DOI: 10.1007/s43440-024-00580-x