RARE DISEASE
Diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma
Synonyms: DIPG
Synonyms: DIPG
Synonyms: DIPG
Drug discovery
5
drugs
With orphan designations
Overview
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor arising in the pons, characterized by diffuse infiltration of glial cells and molecular drivers like H3K27M histone mutations. Diagnosis relies on clinical presentation and MRI findings, with median survival of 8–12 months despite radiotherapy providing temporary symptom relief. No curative therapies exist due to its critical location and resistance to conventional treatments [1][4][11].
Therapies
Radiotherapy: Standard 54–60 Gy fractionated radiation improves symptoms transiently [3][5][16].
Clinical trials: Epigenetic modifiers (e.g., histone deacetylase inhibitors), immunotherapy, and targeted agents (e.g., nimotuzumab) under investigation [7][8][18].
Palliative care: Steroids for edema management and supportive therapies dominate post-progression care [1][12].
Categories: rare neoplastic diseases, rare neurological diseases
Research Papers
1,866 drug discovery papers related to Diffuse intrinsic pontine glioma, with 4 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,866 drug discovery papers related to Diffuse intrinsic pontine glioma, with 4 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | Mapping epigenetic alterations across brain tumor hallmarks.
Central nervous system tumors represent a heterogeneous group of diseases, mainly localized in the brain. Among them, malignant brain tumors represent some of the most aggressive cancers. In adults, only approximately 30% of patients diagnosed with glioblastoma survive beyond two years. Similarly, several pediatric-predominant brain tumors, including medulloblastoma, diffuse intrinsic pontine glioma, and ependymoma, remain among the deadliest solid tumors in children. Therefore, a deeper understanding of brain tumor biology is imperative for the development of more effective therapeutic strategies. Dysregulated epigenetic control has emerged as a critical driver of brain tumor initiation and progression, influencing malignant phenotypes across multiple stages of the disease. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, regulate gene expression programs that contribute to all hallmarks of cancer by modulating the activity of tumor suppressor genes and oncogenes. Given the central role of epigenetics in brain tumorigenesis and the potentially reversible nature of these alterations, epigenetic mechanisms represent particularly attractive therapeutic targets. Although several epigenetic drugs have shown promising results in preclinical and clinical studies, their clinical application remains constrained by a limited knowledge of the brain tumor epigenome and by challenges related to tumor location and drug delivery. In this review, we summarize key epigenetically regulated genes and dysregulated microRNAs across major brain tumor types and link these alterations to specific cancer hallmarks. We further highlight representative examples of epigenetic therapies whose effects converge on hallmark-associated oncogenic processes.
2026-07-03 | Tunable Nanoparticle Thin-Film Reveals Distance Dependence of Auger-Mediated Radiation Enhancement in Diffuse Midline Glioma.
Metallic nanoparticles (NPs) enhance radiotherapy through photoelectric absorption and Auger electron cascades, yet the effective spatial range over which these low-energy electrons induce biological damage remains poorly defined. Quantifying nanoscale energy deposition is essential for rational therapeutic design and safe clinical translation. Here, we establish a self-assembled polyelectrolyte-nanoparticle-cell architecture enabling nanometer-precision control of NP-cell separation (25-100 nm) to directly probe distance-dependent radiation enhancement. Layer-by-layer assembly produced uniform interfaces confirmed by spectroscopy, ellipsometry, electron microscopy, atomic force microscopy, and microgravimetry. Using human microglial (HMC3) and diffuse intrinsic pontine glioma (SU-DIPG-IV) cells, we quantified intracellular reactive oxygen species generation and γH2AX-marked DNA double-strand breaks following 137Cs γ-irradiation. Cells positioned 25.9 nm from the NP layer exhibited significantly increased DNA damage relative to NP-free controls, whereas damage progressively decreased with increasing separation, yielding a 250% differential effect between 25.9 and 97.5 nm. Modality-dependent attenuation profiles were observed across γ-ray, X-ray, and electron irradiation. These findings define the effective nanoscale interaction radius governing NP-mediated Auger enhancement and establish a technique for the interrogation of light-matter interactions for therapeutic energy deposition.
2026-07-01 | Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.
Central nervous system (CNS) tumors are the deadliest cancers in children, highlighting the need for new therapies. The tumor-associated antigens (TAAs) WT1, PRAME and survivin are widely expressed by these tumors, and a manufacturing technique has been developed to target these intracellular TAAs using autologous, nongenetically engineered T cells. Here we therefore conducted ReMIND, an open-label, phase 1 adaptive dose-finding study to determine the safety/feasibility of autologous, systemically administered trivalent T cells targeting WT1, PRAME and survivin in children with CNS tumors. Eligible patients had newly diagnosed diffuse intrinsic pontine glioma without lymphodepletion (arm A, n = 16 enrolled, n = 11 infused) and relapsed/recurrent nonbrainstem CNS malignancies without (arm B, n = 28 enrolled, n = 18 infused) or with (arm C, n = 7 enrolled, n = 4 infused) lymphodepletion. Primary end points were safety, feasibility and maximum tolerated dose determination; secondary end points included preliminary efficacy and immunobiological correlates, including in vivo TAA-T persistence and systemic immune activation. Dose level 3 (8 × 107 cells per m2 per dose) was determined as the maximum tolerated dose. Treatment was well tolerated with fatigue and headache being the most common adverse events, although two possibly related serious adverse events of tumor swelling occurred. One grade 5 event in a patient with diffuse intrinsic pontine glioma with hydrocephalus, tumor edema and respiratory failure was categorized as a dose-limiting toxicity. Median overall survival for arm A was 13.7 months from diagnosis (range, 6.2-32.0) and median progression-free survival for arms B/C was 5.0 months from infusion (range, 0.5-51.6). Three patients in arms B/C are alive without disease at 31.8, 41.2 and 51.6 months without further treatment, including one complete response. This trial met safety/feasibility primary end points with some preliminary signals of efficacy. ClinicalTrials.gov registration: NCT03652545 .
2026-07-11 | Mapping epigenetic alterations across brain tumor hallmarks.
Central nervous system tumors represent a heterogeneous group of diseases, mainly localized in the brain. Among them, malignant brain tumors represent some of the most aggressive cancers. In adults, only approximately 30% of patients diagnosed with glioblastoma survive beyond two years. Similarly, several pediatric-predominant brain tumors, including medulloblastoma, diffuse intrinsic pontine glioma, and ependymoma, remain among the deadliest solid tumors in children. Therefore, a deeper understanding of brain tumor biology is imperative for the development of more effective therapeutic strategies. Dysregulated epigenetic control has emerged as a critical driver of brain tumor initiation and progression, influencing malignant phenotypes across multiple stages of the disease. Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, regulate gene expression programs that contribute to all hallmarks of cancer by modulating the activity of tumor suppressor genes and oncogenes. Given the central role of epigenetics in brain tumorigenesis and the potentially reversible nature of these alterations, epigenetic mechanisms represent particularly attractive therapeutic targets. Although several epigenetic drugs have shown promising results in preclinical and clinical studies, their clinical application remains constrained by a limited knowledge of the brain tumor epigenome and by challenges related to tumor location and drug delivery. In this review, we summarize key epigenetically regulated genes and dysregulated microRNAs across major brain tumor types and link these alterations to specific cancer hallmarks. We further highlight representative examples of epigenetic therapies whose effects converge on hallmark-associated oncogenic processes.
2026-07-03 | Tunable Nanoparticle Thin-Film Reveals Distance Dependence of Auger-Mediated Radiation Enhancement in Diffuse Midline Glioma.
Metallic nanoparticles (NPs) enhance radiotherapy through photoelectric absorption and Auger electron cascades, yet the effective spatial range over which these low-energy electrons induce biological damage remains poorly defined. Quantifying nanoscale energy deposition is essential for rational therapeutic design and safe clinical translation. Here, we establish a self-assembled polyelectrolyte-nanoparticle-cell architecture enabling nanometer-precision control of NP-cell separation (25-100 nm) to directly probe distance-dependent radiation enhancement. Layer-by-layer assembly produced uniform interfaces confirmed by spectroscopy, ellipsometry, electron microscopy, atomic force microscopy, and microgravimetry. Using human microglial (HMC3) and diffuse intrinsic pontine glioma (SU-DIPG-IV) cells, we quantified intracellular reactive oxygen species generation and γH2AX-marked DNA double-strand breaks following 137Cs γ-irradiation. Cells positioned 25.9 nm from the NP layer exhibited significantly increased DNA damage relative to NP-free controls, whereas damage progressively decreased with increasing separation, yielding a 250% differential effect between 25.9 and 97.5 nm. Modality-dependent attenuation profiles were observed across γ-ray, X-ray, and electron irradiation. These findings define the effective nanoscale interaction radius governing NP-mediated Auger enhancement and establish a technique for the interrogation of light-matter interactions for therapeutic energy deposition.
2026-07-01 | Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.
Central nervous system (CNS) tumors are the deadliest cancers in children, highlighting the need for new therapies. The tumor-associated antigens (TAAs) WT1, PRAME and survivin are widely expressed by these tumors, and a manufacturing technique has been developed to target these intracellular TAAs using autologous, nongenetically engineered T cells. Here we therefore conducted ReMIND, an open-label, phase 1 adaptive dose-finding study to determine the safety/feasibility of autologous, systemically administered trivalent T cells targeting WT1, PRAME and survivin in children with CNS tumors. Eligible patients had newly diagnosed diffuse intrinsic pontine glioma without lymphodepletion (arm A, n = 16 enrolled, n = 11 infused) and relapsed/recurrent nonbrainstem CNS malignancies without (arm B, n = 28 enrolled, n = 18 infused) or with (arm C, n = 7 enrolled, n = 4 infused) lymphodepletion. Primary end points were safety, feasibility and maximum tolerated dose determination; secondary end points included preliminary efficacy and immunobiological correlates, including in vivo TAA-T persistence and systemic immune activation. Dose level 3 (8 × 107 cells per m2 per dose) was determined as the maximum tolerated dose. Treatment was well tolerated with fatigue and headache being the most common adverse events, although two possibly related serious adverse events of tumor swelling occurred. One grade 5 event in a patient with diffuse intrinsic pontine glioma with hydrocephalus, tumor edema and respiratory failure was categorized as a dose-limiting toxicity. Median overall survival for arm A was 13.7 months from diagnosis (range, 6.2-32.0) and median progression-free survival for arms B/C was 5.0 months from infusion (range, 0.5-51.6). Three patients in arms B/C are alive without disease at 31.8, 41.2 and 51.6 months without further treatment, including one complete response. This trial met safety/feasibility primary end points with some preliminary signals of efficacy. ClinicalTrials.gov registration: NCT03652545 .
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Drug Discovery Landscape
5 orphan drug designations for Diffuse intrinsic pontine glioma.
5 orphan drug designations for Diffuse intrinsic pontine glioma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Humanised IgG1 kappa monoclonal antibody against erythropoietin isoform EV-3 | antibodies | EMA | 2026-02-23 | — | Andremacon S.r.l. |
Iniparib | small molecules | EMA | 2025-12-09 | — | Raremoon Consulting Esp S.L. |
1,2:5,6-dianhydrogalactitol | small molecules | FDA | 2022-12-14 | — | Kintara Therapeutics, Inc. |
dimethylaminomicheliolide Fumarate | small molecules | FDA | 2022-11-03 | — | Accendatech AU Pty Ltd. |
A10 & AS2-1 Antineoplaston | peptides | FDA | 2004-09-03 | — | Burzynski Research Institute, Inc. |
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