Trial reportClinical epigenetics2023
Aberrant JAK-STAT signaling-mediated chromatin remodeling impairs the sensitivity of NK/T-cell lymphoma to chidamide.
Trial report in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02878278 (Research About the Differences Between Chidamide Taken Daily and Twice a Week in Pharmacokinetics), which is not on this map. Cited by 16 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.
Research About the Differences Between Chidamide Taken Daily and Twice a Week in Pharmacokinetics
Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.Signal transduction and targeted therapy · 2024Trial
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- Molecular mechanisms of Epstein-Barr Virus in the pathogenesis of lymphomas and new opportunities for precision medicine.Discover oncology · 2026Review
- Unraveling the many faces of angioimmunoblastic T-cell lymphoma: clinical, pathological, and molecular heterogeneity.Annals of hematology · 2026Review
- Expressional and prognostic value of cytokine receptor-like factor 3 in liver hepatocellular carcinoma patients via integrated bioinformatics analyses and experiments.SAGE open medicine · 2026Article
- Pediatric extranasal, EBV-negative, extranodal natural killer/T-cell lymphoma; case report.Pathology oncology research : POR · 2026Article
- Real-world efficacy and safety of golidocitinib in 3 patients with relapsed/refractory peripheral T-cell lymphoma.Frontiers in oncology · 2026Article
- Single-cell sequencing uncovers clonal dynamics profiles and therapeutic resistance biomarkers in relapsed and refractory peripheral T-cell lymphoma.Frontiers in immunology · 2026Article
- Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma.Annals of hematology · 2025Article
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.Recent patents on anti-cancer drug discovery · 2025Article
- Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.Cancer communications (London, England) · 2024Review
- Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.Journal of hematology & oncology · 2024Review
- The pharmacoepigenetic paradigm in cancer treatment.Frontiers in pharmacology · 2024Review
- Sustained yet non-curative response to lenalidomide in relapsed angioimmunoblastic T-cell lymphoma with acquired chidamide resistance: a case report with 10-year follow-up, genetic insights and literature review.Frontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
35 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNatural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's lymphoma (NHL) with a poor prognosis and limited therapeutic options. Therefore, there is an urgent need to exploit potential novel therapeutic targets for the treatment of NKTL. Histone deacetylase (HDAC) inhibitor chidamide was recently approved for treating relapsed/refractory peripheral T-cell lymphoma (PTCL) patients. However, its therapeutic efficacy in NKTL remains unclear.
methodsWe performed a phase II clinical trial to evaluate the efficacy of chidamide in 28 relapsed/refractory NKTL patients. Integrative transcriptomic, chromatin profiling analysis and functional studies were performed to identify potential predictive biomarkers and unravel the mechanisms of resistance to chidamide. Immunohistochemistry (IHC) was used to validate the predictive biomarkers in tumors from the clinical trial.
resultsWe demonstrated that chidamide is effective in treating relapsed/refractory NKTL patients, achieving an overall response and complete response rate of 39 and 18%, respectively. In vitro studies showed that hyperactivity of JAK-STAT signaling in NKTL cell lines was associated with the resistance to chidamide. Mechanistically, our results revealed that aberrant JAK-STAT signaling remodels the chromatin and confers resistance to chidamide. Subsequently, inhibition of JAK-STAT activity could overcome resistance to chidamide by reprogramming the chromatin from a resistant to sensitive state, leading to synergistic anti-tumor effect in vitro and in vivo. More importantly, our clinical data demonstrated that combinatorial therapy with chidamide and JAK inhibitor ruxolitinib is effective against chidamide-resistant NKTL. In addition, we identified TNFRSF8 (CD30), a downstream target of the JAK-STAT pathway, as a potential biomarker that could predict NKTL sensitivity to chidamide.
conclusionsOur study suggests that chidamide, in combination with JAK-STAT inhibitors, can be a novel targeted therapy in the standard of care for NKTL.
trial registrationClinicalTrials.gov, NCT02878278. Registered 25 August 2016, https://clinicaltrials.gov/ct2/show/NCT02878278.
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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.