ArticleOncotarget2017
Small molecules targeting histone demethylase genes (KDMs) inhibit growth of temozolomide-resistant glioblastoma cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- The KDM-family inhibitor JIB-04 sensitizes AML cells to venetoclax by inducing a ferroptosis-like phenotype.Blood neoplasia · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Analysis of cerebrospinal fluid tumor-derived DNA to obviate biopsy of IDH-mutant brainstem glioma in an adult.The journal of liquid biopsy · 2025Article
- Histone demethylase inhibitors: developmental insights and current status.Future medicinal chemistry · 2025Review
- HADHA-mediated regulation of JAK/STAT3 signaling in glioblastoma: a metabolic-epigenetic axis.Cell death discovery · 2025Article
- Epigenetic targeting of MECOM/KRAS axis by JIB-04 impairs tumorigenesis and cisplatin resistance in MECOM-amplified ovarian cancer.Cell death discovery · 2025Article
- Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications.Frontiers in epigenetics and epigenomics · 2025Review
- The epigenetic mechanisms involved in the treatment resistance of glioblastoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Diamond Nanoparticles Suppress Migration of T98G Glioblastoma Cells by Targeting ECM-Integrin Interactions and Intracellular Signaling, Leading to Extensive Proteome Alterations.Nanotechnology, science and applications · 2025Article
- A Review of Therapeutic Agents Given by Convection-Enhanced Delivery for Adult Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Targeting Alpha-Ketoglutarate Disruption Overcomes Immunoevasion and Improves PD-1 Blockade Immunotherapy in Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The role of histone H3 lysine demethylases in glioblastoma.Cancer metastasis reviews · 2023Review
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
- The function of histone methylation and acetylation regulators in GBM pathophysiology.Frontiers in oncology · 2023Review
- Dieting reverses histone methylation and hypothalamic AgRP regulation in obese rats.Frontiers in endocrinology · 2023Article
- JMJD family proteins in cancer and inflammation.Signal transduction and targeted therapy · 2022Review
- Recent Advances with KDM4 Inhibitors and Potential Applications.Journal of medicinal chemistry · 2022Review
- JIB-04, a Pan-Inhibitor of Histone Demethylases, Targets Histone-Lysine-Demethylase-Dependent AKT Pathway, Leading to Cell Cycle Arrest and Inhibition of Cancer Stem-Like Cell Properties in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2022Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells.Because of its lower IC50, we focused on JIB 04 that targets KDM5A and other KDMs as well. We have shown that this molecule activates autophagic and apoptotic pathways, interferes with cell cycle progression, inhibits cell clonogenicity and dephosphorylates Akt thus inactivating a potent pro-survival pathway. We performed combination temozolomide/JIB 04 in vitro treatments showing that these two molecules, under certain conditions, have a strong synergic effect and we hypothesize that JIB 04 intercepts the cells that escape the G2 block exerted by TMZ. Finally we studied the permeability of JIB 04 across the blood-brain barrier and found that this molecule reaches bioactive concentration in the brain; furthermore a pilot in vivo experiment in an orthotopic GB xenograft model showed a trend toward longer survival in treated mice with an Hazard Ratio of 0.5.In conclusion we propose that the combination between cytotoxic drugs and molecules acting on the epigenetic landscape may offer the opportunity to develop new therapies for this invariably lethal disease.
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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.