ArticlePloS one2014
Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- A cross-tissue transcriptomic approach decodes glucocorticoid receptor-dependent links to human metabolic phenotypes.BMC genomics · 2025Article
- Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism.Molecular cancer therapeutics · 2024Article
- SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.Cancers · 2023Article
- Monoclonal antibodies binding to different epitopes of CD20 differentially sensitize DLBCL to different classes of chemotherapy.Frontiers in oncology · 2023Article
- Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer.Breast cancer research : BCR · 2022Article
- Chronic Inflammation Pathway NF-κB Cooperates with Epigenetic Reprogramming to Drive the Malignant Progression of Glioblastoma.International journal of biological sciences · 2022Article
- Histone Modifying Enzymes as Targets for Therapeutic Intervention in Oesophageal Adenocarcinoma.Cancers · 2021Review
- Deregulation of Transcriptional Enhancers in Cancer.Cancers · 2021Review
- EZH2 inhibition by tazemetostat: mechanisms of action, safety and efficacy in relapsed/refractory follicular lymphoma.Future oncology (London, England) · 2021Article
- Treating lymphoma is now a bit EZ-er.Blood advances · 2021Review
- Effects of acute heat stress on protein expression and histone modification in the adrenal gland of male layer-type country chickens.Scientific reports · 2021Article
- Pathogenic Impacts of Dysregulated Polycomb Repressive Complex Function in Hematological Malignancies.International journal of molecular sciences · 2020Review
- EZH2: a novel target for cancer treatment.Journal of hematology & oncology · 2020Review
- Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer.Nature genetics · 2020Article
- Article
- Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer.Nature medicine · 2019Review
- Polycomb complexes in normal and malignant hematopoiesis.The Journal of cell biology · 2019Review
- The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma.Journal of cellular physiology · 2018Review
- Oncogenic roles of enhancer of zeste homolog 1/2 in hematological malignancies.Cancer science · 2018Review
- Enhancer of zeste homolog 2 (EZH2) inhibitors.Leukemia & lymphoma · 2018Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.
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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.