ArticleCell reports2018
Jumonji Inhibitors Overcome Radioresistance in Cancer through Changes in H3K4 Methylation at Double-Strand Breaks.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 112 citations in OpenAlex.
- The role of KDM5B in creating synthetic vulnerabilities in combination with radiotherapy in melanoma cells.Cell communication and signaling : CCS · 2026Article
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- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Roles of KDM5 demethylases in therapeutic resistance of cancers.Epigenetics & chromatin · 2025Review
- Abacavir enhances the efficacy of doxorubicin via inhibition of histone demethylase KDM5B in breast cancer.Scientific reports · 2025Article
- Epigenetic targeting of MECOM/KRAS axis by JIB-04 impairs tumorigenesis and cisplatin resistance in MECOM-amplified ovarian cancer.Cell death discovery · 2025Article
- The WWP1-JARID1B axis sustains acute myeloid leukemia chemoresistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanisms Underlying Radioresistance and Reversal Strategies in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- BIX01294 suppresses PDAC growth through inhibition of glutaminase-mediated glutathione dynamics.Molecular metabolism · 2025Article
- Lipoylation inhibition enhances radiation control of lung cancer by suppressing homologous recombination DNA damage repair.Science advances · 2025Article
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- PTIP epigenetically regulates DNA damage-induced cell cycle arrest by upregulating PRDM1.Scientific reports · 2024Article
- Triple Combinations of Histone Lysine Demethylase Inhibitors with PARP1 Inhibitor-Olaparib and Cisplatin Lead to Enhanced Cytotoxic Effects in Head and Neck Cancer Cells.Biomedicines · 2024Article
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- Glutamine-mediated epigenetic regulation of cFLIP underlies resistance to TRAIL in pancreatic cancer.Experimental & molecular medicine · 2024Article
- Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling.Signal transduction and targeted therapy · 2023Article
- Recognition of Histone H3 Methylation States by the PHD1 Domain of Histone Demethylase KDM5A.ACS chemical biology · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
We have uncovered a role for Jumonji inhibitors in overcoming radioresistance through KDM5B inhibition. Pharmacological blockade of Jumonji demethylases with JIB-04 leads to specific accumulation of H3K4me3 at sites marked by γH2AX and impaired recruitment of DNA repair factors, preventing resolution of damage and resulting in robust sensitization to radiation therapy. In DNA-repair-proficient cancer cells, knockdown of the H3K4me3 demethylase KDM5B, but not other Jumonji enzymes, mimics pharmacological inhibition, and KDM5B overexpression rescues this phenotype and increases radioresistance. The H3K4me3 demethylase inhibitor PBIT also sensitizes cancer cells to radiation, while an H3K27me3 demethylase inhibitor does not. In vivo co-administration of radiation with JIB-04 significantly prolongs the survival of mice with tumors even long after cessation of treatment. In human patients, lung squamous cell carcinomas highly expressing KDM5B respond poorly to radiation. Thus, we propose the use of Jumonji KDM inhibitors as potent radiosensitizers.
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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.