ArticleNeoplasia (New York, N.Y.)2019
Preclinical Studies Support Combined Inhibition of BET Family Proteins and Histone Deacetylases as Epigenetic Therapy for Cutaneous T-Cell Lymphoma.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- Co-expression of CD30 and SLFN11 serves as a dual biomarker for the treatment of cutaneous T-cell lymphoma.NAR cancer · 2025Article
- JAK2 46/1 (GGCC) Haplotype in Oncogenesis, as Risk Stratifier, and Indicator for Drug Resistance in Myeloproliferative Neoplasms.International journal of molecular sciences · 2025Review
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- A Combination of CPI-0610 and SAHA Induces Apoptosis through STAT3 and p38 Signalling Pathways in Diffuse Large B-cell Lymphoma Cells.Current medicinal chemistry · 2025Article
- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- FISH Panel for Leukemic Cutaneous T-Cell Lymphoma: Extended Patient Cohort Correlation with Blood Involvement and Clinical Outcomes.JID innovations : skin science from molecules to population health · 2023Article
- The Robust Tumoricidal Effects of Combined BET/HDAC Inhibition in Cutaneous T-Cell Lymphoma Can Be Reproduced by ΔNp73 Depletion.The Journal of investigative dermatology · 2022Article
- Super-enhancer-controlled positive feedback loop BRD4/ERα-RET-ERα promotes ERα-positive breast cancer.Nucleic acids research · 2022Article
- Dual HDAC/BRD4 Inhibitors Relieves Neuropathic Pain by Attenuating Inflammatory Response in Microglia After Spared Nerve Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Novel Targeted Therapies for T-Cell Malignancies.Cancers · 2022Article
- Epigenetics of Cutaneous T-Cell Lymphomas.International journal of molecular sciences · 2022Review
- Article
- Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy.European journal of medicinal chemistry · 2021Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- Epigenetics in the Pathogenesis and Treatment of Cutaneous T-Cell Lymphoma.Frontiers in oncology · 2021Review
- Novel targeted therapies of T cell lymphomas.Journal of hematology & oncology · 2020Review
- Targeting complexes of super-enhancers is a promising strategy for cancer therapy.Oncology letters · 2020Review
- Article
- Epigenetic regulation of defense genes by histone deacetylase1 in human cell line-derived macrophages promotes intracellular survival of Leishmania donovani.PLoS neglected tropical diseases · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Advanced-stage cutaneous T-cell lymphoma (CTCL) is usually a fatal malignancy despite optimal use of currently available treatments. In this preclinical study of novel CTCL therapy, we performed in vitro and ex vivo experiments to determine the efficacy of combination treatment with a panel of BET bromodomain inhibitors (BETi) (JQ1, OTX015, CPI-0610, I-BET762) and HDAC inhibitors (HDACi) (SAHA/Vorinostat, Romidepsin). BETi/HDACi combinations were synergistic (combination index <1) against cell viability and induced G0/G1 cell cycle arrest. Apoptosis was uniformly enhanced. From a mechanistic standpoint, proliferative drivers c-Myc, Cyclin D1, NFkB, and IL-15Rα were reduced. Inhibitory CDKN1A was increased. CDKN1B, IL-7R, IL-17Rα, STAT3, and STAT5 alterations varied. There were significant increases in extrinsic apoptotic pathway death receptors and ligands (FasL, DR4, DR5, TRAIL, and TNFR1). At clinically tolerable levels of single agents, Romidepsin (1 nM) + OTX015 (125 nM) induced the greatest apoptosis (60%_80%) at 96 hours. Ex vivo studies of leukemic CTCL cells obtained from patients with Sezary syndrome also showed higher levels of apoptosis (about 60%-90%) in response to combination treatments relative to single agents. In contrast, combination treatment of normal CD4+ T cells induced only minimal apoptosis (<10%). Our findings show that the mechanism of action of BETi/HDACi therapy in CTCL involves induction of both cell cycle arrest and apoptosis with reduced proliferative drivers and enhanced expression of apoptotic extrinsic pathway death receptors and ligands. Relative to single agents, the superior anti-CTCL effects of BETi/HDACi combinations in vitro and ex vivo provide a rationale for clinical trials exploring their efficacy as therapy for CTCL.
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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.