ArticleOncotarget2018
EZH2 inhibitors sensitize myeloma cell lines to panobinostat resulting in unique combinatorial transcriptomic changes.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Genetic, epigenetic, and molecular determinants of multiple myeloma and precursor plasma cell disorders: a pathophysiological overview.Medical oncology (Northwood, London, England) · 2025Review
- NAT10 MediatesJournal of Cancer · 2024Article
- A de novo missense variant in EZH1 associated with developmental delay exhibits functional deficits in Drosophila melanogaster.Genetics · 2023Article
- One Omics Approach Does Not Rule Them All: The Metabolome and the Epigenome Join Forces in Haematological Malignancies.Epigenomes · 2021Review
- Review
- HighJournal of Cancer · 2021Article
- Genetic Predictors of Mortality in Patients with Multiple Myeloma.The application of clinical genetics · 2021Review
- Role of Polycomb Complexes in Normal and Malignant Plasma Cells.International journal of molecular sciences · 2020Review
- Epigenetic Aberrations in Multiple Myeloma.Cancers · 2020Review
- Design of First-in-Class Dual EZH2/HDAC Inhibitor: Biochemical Activity and Biological Evaluation in Cancer Cells.ACS medicinal chemistry letters · 2020Article
- Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy.Molecular cancer · 2020Review
- Chidamide epigenetically represses autophagy and exerts cooperative antimyeloma activity with bortezomib.Cell death & disease · 2020Article
- TAZ functions as a tumor suppressor in multiple myeloma by downregulating MYC.Blood advances · 2019Article
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
- Review
- Review
- Osteoblast suppression in multiple myeloma bone disease.Journal of bone oncology · 2018Review
- Targeting EZH2 in Multiple Myeloma-Multifaceted Anti-Tumor Activity.Epigenomes · 2018Article
- EZH2 as a therapeutic target for multiple myeloma and other haematological malignancies.Biomarker research · 2018Review
- The Epigenome in Multiple Myeloma: Impact on Tumor Cell Plasticity and Drug Response.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation. Pre-treatment with EZH2 inhibitors greatly enhanced the sensitivity of HMCLs to the pan-HDAC inhibitor panobinostat in nearly all cases regardless of single agent EZH2 inhibitor sensitivity. Transcriptomic profiling revealed large-scale transcriptomic alteration by EZH2 inhibition highly enriched for cancer-related pathways. Combination treatment greatly increased the scale of gene expression change with a large portion of differentially expressed genes being unique to the combination. Transcriptomic analysis demonstrated that combination treatment further perturbed oncogenic pathways and signaling nodes consistent with an antiproliferative/pro-apoptotic state. We conclude that combined inhibition of HDAC and EZH2 inhibitors is a promising therapeutic strategy to broadly target the epigenetic landscape of aggressive MM.
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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.