Diffuse Intrinsic Pontine Glioma

Valvi, Santosh; Gottardo, Nicholas

doi:10.5772/intechopen.78578

Cited by 4 publications

(3 citation statements)

References 192 publications

(16 reference statements)

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“…Although in a survival prediction model, DIPG spread to the medulla and midbrain was not a significant prognostic value (3), in a different study extrapontine extension was shown to be more common in short-term compared to longterm survivors (2). This impact on DIPG prognosis can be due to the ability of invading DIPG cells to distort, displace, and destroy nerve fiber tracts (4). For instance, specific symptoms like impairment of gait, coordination, and speech, are thought to be associated with invasion of tumor cells to the adjacent cerebellum (5).…”

Section: Introductionmentioning

confidence: 98%

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

et al. 2020

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Diffuse Intrinsic Pontine Glioma (DIPG) is a rare, highly aggressive pediatric brain tumor that originates in the pons. DIPG is untreatable and universally fatal, with a median life expectancy of less than a year. Resection is not an option, due to the anatomical location of the tumor, radiotherapy has limited effect and no chemotherapeutic or targeted treatment approach has proven to be successful. This poor prognosis is partly attributed to the tumor's highly infiltrative diffuse and invasive spread. Thus, targeting the invasive behavior of DIPG has the potential to be of therapeutic value. In order to target DIPG invasion successfully, detailed mechanistic knowledge on the underlying drivers is required. Here, we review both DIPG tumor cell's intrinsic molecular processes and extrinsic environmental factors contributing to DIPG invasion. Importantly, DIPG represents a heterogenous disease and through advances in whole-genome sequencing, different subtypes of disease based on underlying driver mutations are now being recognized. Recent evidence also demonstrates intra-tumor heterogeneity in terms of invasiveness and implies that highly infiltrative tumor subclones can enhance the migratory behavior of neighboring cells. This might partially be mediated by "tumor microtubes," long membranous extensions through which tumor cells connect and communicate, as well as through the secretion of extracellular vesicles. Some of the described processes involved in invasion are already being targeted in clinical trials. However, more research into the mechanisms of DIPG invasion is urgently needed and might result in the development of an effective therapy for children suffering from this devastating disease. We discuss the implications of newly discovered invasive mechanisms for therapeutic targeting and the challenges therapy development face in light of disease in the developing brain.

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Section: Introductionmentioning

confidence: 98%

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

et al. 2020

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“…In this subsection, we will focus primarily on DMGs: they are of particular interest for immunotherapy development given their dismal responses to existing treatments. Approximately 70-80% of DMGs are primarily driven by epigenetic mis-regulation, wherein mutations to the H3 histone-most often a lysine to methionine mutation (K27M)-disrupt the packaging of replicated DNA and its integration into transcriptionally active regions of the genome [143,144]. Because of their highly diffuse, invasive, and pernicious growth that distorts local brain tissue, the available knowledge on the TIME relies heavily on autopsy samples, and more limited data are available on the nature of the DMG TIME at earlier pathophysiological stages and prior to treatment [145].…”

Section: High-grade Pediatric Gliomasmentioning

confidence: 99%

Pediatric Brain Tumours: Lessons from the Immune Microenvironment

2023

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In spite of recent advances in tumour molecular subtyping, pediatric brain tumours (PBTs) remain the leading cause of cancer-related deaths in children. While some PBTs are treatable with favourable outcomes, recurrent and metastatic disease for certain types of PBTs remains challenging and is often fatal. Tumour immunotherapy has emerged as a hopeful avenue for the treatment of childhood tumours, and recent immunotherapy efforts have been directed towards PBTs. This strategy has the potential to combat otherwise incurable PBTs, while minimizing off-target effects and long-term sequelae. As the infiltration and activation states of immune cells, including tumour-infiltrating lymphocytes and tumour-associated macrophages, are key to shaping responses towards immunotherapy, this review explores the immune landscape of the developing brain and discusses the tumour immune microenvironments of common PBTs, with hopes of conferring insights that may inform future treatment design.

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“…DMG is known for its aggressive nature, dismal outcomes, and poor prognosis with a 99% 5-year mortality rate [ 13 ]. Due to the high morbidity associated with surgery in such an eloquent region of the brain and sampling errors associated with biopsies, the treatment options for DMG are confined to either chemotherapy, radiotherapy, or targeted molecular agents, all of which are associated with minimal effectiveness [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Midline Gliomas: A Retrospective Study from a Cancer Center in the Middle East

Al Sharie,

Abu Laban,

Nazzal

et al. 2023

Cancers

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Midline gliomas are tumors that occur in midline structures and can be circumscribed or diffuse. Classical midline structures include the thalamus, brainstem, and spinal cord. Other midline structures include the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum. Diffuse midline glioma (DMG) is a diffuse glioma that occurs in the classical midline structures, characterized by a specific genetic alteration, and associated with grim outcome. This study was conducted at King Hussein Cancer Center and reviewed the medical records of 104 patients with circumscribed and diffuse gliomas involving midline structures that underwent biopsy between 2005 and 2022. We included a final cohort of 104 patients characterized by a median age of 23 years and a male-to-female ratio of 1.59-to-1. Diffuse high-grade glioma (DHGG) was the most common pathological variant (41.4%), followed by DMG (28.9%). GFAP was positive in most cases (71.2%). Common positive mutations/alterations detected by surrogate immunostains included H3 K27me3 (28.9%), p53 (25.0%), and H3 K27M (20.2%). Age group, type of treatment, and immunohistochemistry were significantly associated with both the location of the tumor and tumor variant (all; p < 0.05). DMGs were predominantly found in the thalamus, whereas circumscribed gliomas were most commonly observed in the spinal cord. None of the diffuse gliomas outside the classical location, or circumscribed gliomas harbored the defining DMG mutations. The median overall survival (OS) for the entire cohort was 10.6 months. Only the tumor variant (i.e., circumscribed gliomas) and radiotherapy were independent prognosticators on multivariate analysis.

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Diffuse Intrinsic Pontine Glioma

Cited by 4 publications

References 192 publications

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

Pediatric Brain Tumours: Lessons from the Immune Microenvironment

Midline Gliomas: A Retrospective Study from a Cancer Center in the Middle East

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