Therapeutic Targets in Diffuse Midline Gliomas—An Emerging Landscape

Hayden, Elisha; Holliday, Holly; Lehmann, Rebecca; Khan, Aaminah; Tsoli, Maria; Rayner, Benjamin S.; Ziegler, David S.

doi:10.3390/cancers13246251

Cited by 26 publications

(19 citation statements)

References 318 publications

(507 reference statements)

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“…The plasticity makes macrophages a therapeutic target for a variety of cancer. [64] In summary, the DIPG tumor microenvironment presents a non-inflammatory state in which T-cell infiltration is minimal and TAMs occupy a major portion of the immune cells, and promoting immune responses by targeting the M1 macrophage phenotype activation mechanism may be a potential strategy to inhibit DIPG growth. DIPG is distributed with diffuse infiltration of the brainstem, and the extracellular matrix (ECM) within the tumor microenvironment may be altered accordingly used to facilitate tumor cell invasion of the brainstem.…”

Section: Activation Of the Tumor Microenvironment As A Potential Ther...mentioning

confidence: 99%

“…The plasticity makes macrophages a therapeutic target for a variety of cancer. [ 64 ] In summary, the DIPG tumor microenvironment presents a non‐inflammatory state in which T‐cell infiltration is minimal and TAMs occupy a major portion of the immune cells, and promoting immune responses by targeting the M1 macrophage phenotype activation mechanism may be a potential strategy to inhibit DIPG growth.…”

Section: Overview Of Brainstem Gliomasmentioning

confidence: 99%

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Brain‐Targeted Exosomes‐Based Drug Delivery System to Overcome the Treatment Bottleneck of Brainstem Glioma

Chen

Shan

Xia

et al. 2023

Adv Funct Materials

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Brain health is the humans’ primary goal in achieving health and longevity. Brainstem glioma (BSG) has a high disability and mortality rate, posing a serious threat to children's brain health. Delivery of drugs to the brainstem is limited by poor tumor targeting and low blood‐brain barrier (BBB) permeability. Thus, it is a great challenge to construct intracranial drug delivery systems with strong biocompatibility, low immunogenicity, and high BBB permeability for the delivery of drugs targeting BSG. Exosomes, as the next generation of novel delivery systems, have been widely used to across the BBB due to their advantages of good biocompatibility, stability, and permeability of the BBB and have made corresponding breakthroughs in targeted drug delivery for CNS diseases. This review summarizes natural, polypeptide functionalized, and physical methods‐assisted brain‐targeted exosomes‐based drug delivery systems, the drug treatment bottleneck of BSG, and highlights the potential of using a brain‐targeted exosomes‐based drug delivery system to overcome the drug treatment bottleneck of BSG. It provides new insights into using exosomes‐based drug delivery for BSG treatment.

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Section: Activation Of the Tumor Microenvironment As A Potential Ther...mentioning

confidence: 99%

Section: Overview Of Brainstem Gliomasmentioning

confidence: 99%

Brain‐Targeted Exosomes‐Based Drug Delivery System to Overcome the Treatment Bottleneck of Brainstem Glioma

Chen

Shan

Xia

et al. 2023

Adv Funct Materials

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“…Diffuse intrinsic pontine glioma (DIPG), now commonly known as diffuse midline glioma (DMG), is a type of glioma that originates from glial cells, the supportive cells that surround and protect neurons in the brain [ 1 ]. DMG/DIPG is a highly aggressive and lethal pediatric cancer that primarily affects children between the ages of 6 and 9 regardless of gender [ 2 3 ]. This type of tumor is characterized by its location in the pons, a part of the brainstem responsible for critical functions such as breathing, heartbeat, and consciousness.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic and Metabolic Changes in Diffuse Intrinsic Pontine Glioma

Park

Chung

2023

Brain Tumor Res Treat

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Diffuse midline glioma (DMG), hitherto known as diffuse intrinsic pontine glioma (DIPG), is a rare and aggressive form of brain cancer that primarily affects children. Although the exact cause of DMG/DIPG is not known, a large proportion of DMG/DIPG tumors harbor mutations in the gene encoding the histone H3 protein, specifically the H3K27M mutation. This mutation decreases the level of H3K27me3, a histone modification that plays a vital role in regulating gene expression through epigenetic regulation. The mutation also alters the function of polycomb repressive complex 2 (PRC2), thereby preventing the repression of genes associated with cancer development. The decrease in H3K27me3 caused by the histone H3 mutation is accompanied by an increase in the level of H3K27ac, a post-translational modification related to active transcription. Dysregulation of histone modification markedly affects gene expression, contributing to cancer development and progression by promoting uncontrolled cell proliferation, tumor growth, and metabolism. DMG/DIPG alters the metabolism of methionine and the tricarboxylic acid cycle, as well as glucose and glutamine uptake. The role of epigenetic and metabolic changes in the development of DMG/DIPG has been studied extensively, and understanding these changes is critical to developing therapies targeting these pathways. Studies are currently underway to identify new therapeutic targets for DMG/DIPG, which may lead to the development of effective treatments for this devastating disease.

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“…Diffuse midline gliomas (DMGs) are one of the most devastating pediatric cancers, representing about 20% of all pediatric central nervous system (CNS) tumors, with approximately 200 to 300 new cases diagnosed each year in the United States [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle

et al. 2022

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Diffuse midline glioma (DMG) is a heterogeneous group of aggressive pediatric brain tumors with a fatal prognosis. The biological hallmark in the major part of the cases is H3K27 alteration. Prognosis remains poor, with median survival ranging from 9 to 12 months from diagnosis. Clinical and radiological prognostic factors only partially change the progression-free survival but they do not improve the overall survival. Despite efforts, there is currently no curative therapy for DMG. Radiotherapy remains the standard treatment with only transitory benefits. No chemotherapeutic regimens were found to significantly improve the prognosis. In the new era of a deeper integration between histological and molecular findings, potential new approaches are currently under investigation. The entire international scientific community is trying to target DMG on different aspects. The therapeutic strategies involve targeting epigenetic alterations, such as methylation and acetylation status, as well as identifying new molecular pathways that regulate oncogenic proliferation; immunotherapy approaches too are an interesting point of research in the oncology field, and the possibility of driving the immune system against tumor cells has currently been evaluated in several clinical trials, with promising preliminary results. Moreover, thanks to nanotechnology amelioration, the development of innovative delivery approaches to overcross a hostile tumor microenvironment and an almost intact blood–brain barrier could potentially change tumor responses to different treatments. In this review, we provide a comprehensive overview of available and potential new treatments that are worldwide under investigation, with the intent that patient- and tumor-specific treatment could change the biological inauspicious history of this disease.

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Therapeutic Targets in Diffuse Midline Gliomas—An Emerging Landscape

Cited by 26 publications

References 318 publications

Brain‐Targeted Exosomes‐Based Drug Delivery System to Overcome the Treatment Bottleneck of Brainstem Glioma

Brain‐Targeted Exosomes‐Based Drug Delivery System to Overcome the Treatment Bottleneck of Brainstem Glioma

Epigenetic and Metabolic Changes in Diffuse Intrinsic Pontine Glioma

Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle

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