ArticleNeuro-oncology2019
DECIPHER pooled shRNA library screen identifies PP2A and FGFR signaling as potential therapeutic targets for diffuse intrinsic pontine gliomas.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed.
- A Phase 0 Window of Opportunity Trial of LB100, a Protein Phosphatase 2A Inhibitor, in Patients with Recurrent Gliomas.medRxiv : the preprint server for health sciences · 2025Article
- Advances on the therapeutic potential of cell receptor activation in glioblastoma.Molecular biology reports · 2025Review
- Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma.Cancer letters · 2024Article
- Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies.Cancer letters · 2024Review
- Radiotherapy plus temozolomide with or without anlotinib in H3K27M-mutant diffuse midline glioma: A retrospective cohort study.CNS neuroscience & therapeutics · 2024Article
- Proteomic Analysis Highlights the Impact of the Sphingolipid Metabolizing Enzyme β-Galactosylceramidase on Mitochondrial Plasticity in Human Melanoma.International journal of molecular sciences · 2024Article
- The role of brainstem biopsy and targeted therapies in pediatric diffuse midline glioma/diffuse intrinsic pontine glioma.Frontiers in oncology · 2024Review
- The landscape of cancer-associated transcript fusions in adult brain tumors: a longitudinal assessment in 140 patients with cerebral gliomas and brain metastases.Frontiers in oncology · 2024Article
- Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth.Neuro-oncology · 2023Article
- 3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma.Nature communications · 2023Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- The oncogenic fusion landscape in pediatric CNS neoplasms.Acta neuropathologica · 2022Review
- Repurposing Vandetanib plus Everolimus for the Treatment ofCancer discovery · 2022Article
- Receptor tyrosine kinase (RTK) targeting in pediatric high-grade glioma and diffuse midline glioma: Pre-clinical models and precision medicine.Frontiers in oncology · 2022Review
- Molecular alterations of low-grade gliomas in young patients: Strategies and platforms for routine evaluation.Neuro-oncology practice · 2021Review
- Utilizing preclinical models to develop targeted therapies for rare central nervous system cancers.Neuro-oncology · 2021Review
- Review of PP2A Tumor Biology and Antitumor Effects of PP2A Inhibitor LB100 in the Nervous System.Cancers · 2021Review
- Targeting RTK-PI3K-mTOR Axis in Gliomas: An Update.International journal of molecular sciences · 2021Review
- Therapeutic strategies of recurrent glioblastoma and its molecular pathways 'Lock up the beast'.Ecancermedicalscience · 2021Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiffuse intrinsic pontine gliomas (DIPGs) are highly aggressive pediatric brain tumors that are characterized by a recurrent mutation (K27M) within the histone H3 encoding genes H3F3A and HIST1H3A/B/C. These mutations have been shown to induce a global reduction in the repressive histone modification H3K27me3, which together with widespread changes in DNA methylation patterns results in an extensive transcriptional reprogramming hampering the identification of single therapeutic targets based on a molecular rationale.
methodsWe applied a large-scale gene knockdown approach using a pooled short hairpin (sh)RNA library in combination with next-generation sequencing in order to identify DIPG-specific vulnerabilities. The therapeutic potential of specific inhibitors of candidate targets was validated in a secondary drug screen.
resultsWe identified fibroblast growth factor receptor (FGFR) signaling and the serine/threonine protein phosphatase 2A (PP2A) as top depleted hits in patient-derived DIPG cell cultures and validated their lethal potential by FGF ligand depletion and genetic knockdown of the PP2A structural subunit PPP2R1A. Further, pharmacological inhibition of FGFR and PP2A signaling through ponatinib and LB-100 treatment, respectively, exhibited strong tumor-specific anti-proliferative and apoptotic activity in cultured DIPG cells.
conclusionsOur findings suggest FGFR and PP2A signaling as potential new therapeutic targets for the treatment of DIPGs.
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