ArticleCell cycle (Georgetown, Tex.)2015
The histone demethylase KDM5A is a key factor for the resistance to temozolomide in glioblastoma.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Bibliometric and visualization analysis in the field of epigenetics and glioma (2009-2024).Frontiers in oncology · 2024Pooled it
- Stem-like characteristics across sequentially temozolomide-adapted glioblastoma cell populations with increasing levels of acquired resistance.Molecular biology reports · 2026Article
- Reprogramming temozolomide response in glioblastoma through regulated and immunogenic cell death modalities.Cell death discovery · 2026Review
- KDM5D expression is lost in cisplatin‑resistant neuroblastoma cells.Oncology reports · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Effective approaches in conquering chemoresistance of glioblastoma: potential for nanoformulations.Drug delivery and translational research · 2026Review
- Dissecting the role of epigenetic regulation in oral squamous cell carcinoma microenvironment: mechanisms and therapeutics.Frontiers in immunology · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- An Intrinsically Disordered Region of Histone Demethylase KDM5A Activates Catalysis Through Interactions With the Nucleosomal Acidic Patch and DNA.Journal of molecular biology · 2025Article
- Roles of KDM5 demethylases in therapeutic resistance of cancers.Epigenetics & chromatin · 2025Review
- An intrinsically disordered region of histone demethylase KDM5A activates catalysis through interactions with the nucleosomal acidic patch and DNA.bioRxiv : the preprint server for biology · 2025Article
- Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents.International journal of molecular sciences · 2025Review
- Targeting Metabolic and Epigenetic Vulnerabilities in Glioblastoma with SN-38 and Rabusertib Combination Therapy.International journal of molecular sciences · 2025Article
- Drug-tolerant persister cells in acute myeloid leukemia: pressing challenge and promising new strategies for treatment.Frontiers in medicine · 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
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- Temozolomide (TMZ) in the Treatment of Glioblastoma Multiforme-A Literature Review and Clinical Outcomes.Current oncology (Toronto, Ont.) · 2024Review
- Epigenetic regulation of tumor-immune symbiosis in glioma.Trends in molecular medicine · 2024Review
- Construction and validation of a chromatin regulator-related gene signature for prognostic and therapeutic significance of clear cell renal cell carcinoma.Translational cancer research · 2024Article
- Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notwithstanding current multimodal treatment, including surgery, radiotherapy and chemotherapy with temozolomide (TMZ), median survival of glioblastoma (GBM) patients is about 14 months, due to the rapid emergence of cell clones resistant to treatment. Therefore, understanding the mechanisms underlying chemoresistance is mandatory to improve treatments' outcome. We generated TMZ resistant cells (TMZ-R) from a GBM cell line and from cancer stem cell-enriched cultures isolated from human GBMs. We demonstrated that TMZ resistance is partially reverted by "drug wash-out" suggesting the contribution of epigenetic mechanisms in drug resistance and supporting the possibility of TMZ rechallenge in GBM patients after prior drug exposure. The expression of histone lysine demethylase genes (KDMs) was increased in TMZ-R cells compared to parental cells, and TMZ resistance or restored sensitivity was mimicked by over-expressing or inactivating KDM5A. Methylation and expression of O6-methylguanine-DNA methyltransferase (MGMT) and drug efflux mechanisms were not altered in TMZ-R cells compared to parental TMZ sensitive cells. TMZ-R cells transiently acquired morphologic and molecular characteristics of differentiated tumor cells, features that were lost after drug wash-out. In conclusion, we demonstrated that treatment-induced TMZ resistance in GBM involves epigenetic mechanisms in a subset of slow-cycling and transiently partially differentiated cells that escape drug cytotoxicity, overcome G2 checkpoint and sustain clonal growth. We found that TMZ-R cells are sensitive to histone deacethylase inhibitors (HDACi) that synergize with TMZ. This strong synergism could be exploited to develop novel combined adjuvant therapies for this rapidly progressing and invariably lethal cancer.
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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.