ArticleNPJ precision oncology2024
Combined inhibition of EZH2 and CDK4/6 perturbs endoplasmic reticulum-mitochondrial homeostasis and increases antitumor activity against glioblastoma.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- CDK2/9 blockade remodels chromatin and drives phenotypic plasticity in glioblastoma organoids.Cell communication and signaling : CCS · 2026Article
- Inhibition of PERK signaling suppresses tumor progression and blocks GP73-GRP78-dependent stromal activation in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2026Article
- Enhancer of Zeste Homolog 2 (EZH2): From Glioblastoma Biology to Potential Epigenetic Therapy.International journal of molecular sciences · 2026Review
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Hsa-miR-25-3p Inhibition Sensitizes Patient-Derived Glioblastoma Cells to Temozolomide via β-catenin Downregulation.Cellular and molecular neurobiology · 2026Article
- SLC25A1 upregulation promotes HNSCC cisplatin resistance via H3K27ac-mediated cellular senescence.NPJ precision oncology · 2026Article
- Integrated bioinformatics and experimental validation reveal that CENPF activates mTORC1 signaling to promote colorectal cancer progression.Cancer cell international · 2026Article
- Exploring the dual role of extracellular vesicles in coagulation and immune modulation in glioblastoma.Scientific reports · 2026Article
- Molecular docking and dynamics reveal novel CDK6 inhibitors for targeted glioblastoma therapy.Scientific reports · 2026Article
- Loss ofJournal of Cancer · 2026Article
- A spatiotemporal state-inference framework for adaptive immunotherapy in glioblastoma.Frontiers in oncology · 2026Review
- DEP domain containing 1: a potential oncogenic driver.Biological research · 2025Article
- Citronellol silver nanoconjugates as a therapeutic strategy for glioblastoma through computational and experimental evaluation.Scientific reports · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Validation of an LC-MS/MS Method for the Simultaneous Intracellular Quantification of the CDK4/6 Inhibitor Abemaciclib and the EZH2 Inhibitors GSK126 and Tazemetostat.Pharmaceutics · 2025Article
- Defined Diets Link Iron and α-Linolenic Acid to Cyp1b1 Regulation of Neonatal Liver Development Through Srebp Forms and LncRNA H19.International journal of molecular sciences · 2025Article
- Plasma methylatedFrontiers in medicine · 2025Article
- TMPO-AS1-hsa-let-7b-5p-EZH2-RNA network predicts poor survival in basal-like breast cancer patients.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2025Article
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
He, we show that combined use of the EZH2 inhibitor GSK126 and the CDK4/6 inhibitor abemaciclib synergistically enhances antitumoral effects in preclinical GBM models. Dual blockade led to HIF1α upregulation and CalR translocation, accompanied by massive impairment of mitochondrial function. Basal oxygen consumption rate, ATP synthesis, and maximal mitochondrial respiration decreased, confirming disrupted endoplasmic reticulum-mitochondrial homeostasis. This was paralleled by mitochondrial depolarization and upregulation of the UPR sensors PERK, ATF6α, and IRE1α. Notably, dual EZH2/CDK4/6 blockade also reduced 3D-spheroid invasion, partially inhibited tumor growth in ovo, and led to impaired viability of patient-derived organoids. Mechanistically, this was due to transcriptional changes in genes involved in mitotic aberrations/spindle assembly (Rb, PLK1, RRM2, PRC1, CENPF, TPX2), histone modification (HIST1H1B, HIST1H3G), DNA damage/replication stress events (TOP2A, ATF4), immuno-oncology (DEPDC1), EMT-counterregulation (PCDH1) and a shift in the stemness profile towards a more differentiated state. We propose a dual EZH2/CDK4/6 blockade for further investigation.
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Registered trials
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