ArticleCell death & disease2020
Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells.PloS one · 2026Article
- Synergistic antitumor effect of HMGB2 targeting combined with MDM2 inhibitor in diffuse intrinsic pontine glioma therapy.Frontiers in oncology · 2026Article
- A live cell biosensor protocol for high-resolution screening of therapy-resistant cancer cells.bioRxiv : the preprint server for biology · 2025Article
- Safely Targeting Cancer, the Wound That Never Heals, Utilizing CBP/Beta-Catenin Antagonists.Cancers · 2025Article
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- Super enhancer lncRNAs: a novel hallmark in cancer.Cell communication and signaling : CCS · 2024Review
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- Novel insights on genetics and epigenetics as clinical targets for paediatric astrocytoma.Clinical and translational medicine · 2024Review
- Article
- Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential.Journal of traditional and complementary medicine · 2024Article
- Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer.Frontiers in pharmacology · 2024Review
- Targeting Wnt signaling for improved glioma immunotherapy.Frontiers in immunology · 2024Article
- Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics.Hereditas · 2023Article
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
- Therapeutic avenues for targeting treatment challenges of diffuse midline gliomas.Neoplasia (New York, N.Y.) · 2023Review
- Oncogenic super-enhancers in cancer: mechanisms and therapeutic targets.Cancer metastasis reviews · 2023Review
- Review
- A novel CDK4/6 inhibitor combined with irradiation demonstrates potent anti-tumor efficacy in diffuse midline glioma.Journal of neuro-oncology · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. Hyperacetylation in DIPG favors the action of the Bromodomain and Extra-Terminal (BET) protein BRD4, and leads to the reprogramming of the enhancer landscape contributing to the activation of DIPG super enhancer-driven oncogenes. The activity of the acetyltransferase CREB-binding protein (CBP) is enhanced by BRD4 and associated with acetylation of nucleosomes at super enhancers (SE). In addition, CBP contributes to transcriptional activation through its function as a scaffold and protein bridge. Monotherapy with either a CBP (ICG-001) or BET inhibitor (JQ1) led to the reduction of tumor-related characteristics. Interestingly, combined treatment induced strong cytotoxic effects in H3.3K27M-mutated DIPG cell lines. RNA sequencing and chromatin immunoprecipitation revealed that these effects were caused by the inactivation of DIPG SE-controlled tumor-related genes. However, single treatment with ICG-001 or JQ1, respectively, led to activation of a subgroup of detrimental super enhancers. Combinatorial treatment reversed the inadvertent activation of these super enhancers and rescued the effect of ICG-001 and JQ1 single treatment on enhancer-driven oncogenes in H3K27M-mutated DIPG, but not in H3 wild-type pedHGG cells. In conclusion, combinatorial treatment with CBP and BET inhibitors is highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.