ArticleClinical epigenetics2023
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 21 citations in OpenAlex.
- Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial.Nature medicine · 2024Trial
- Targeting the Epigenome in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Clinical activity of chidamide-containing regimens after prior PD-1-based therapy in two patients with microsatellite-stable metastatic colorectal cancer: a case series and narrative review.Frontiers in oncology · 2026Article
- Epigenetic modulation of CTCs as a novel therapeutic target in oncology.Molecular and cellular biochemistry · 2026Review
- Cancer Reversion Therapy: Prospects, Progress and Future Directions.Current issues in molecular biology · 2025Review
- Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.Cancer innovation · 2025Review
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics.Molecular cancer · 2025Review
- Integrating gene demethylation and immune modulation: PD-1 nanovesicles as a dual-action therapy for NSCLC.Materials today. Bio · 2025Article
- Epigenetic regulators combined with tumour immunotherapy: current status and perspectives.Clinical epigenetics · 2025Review
- Salvage treatment of a metastatic colorectal cancer with pMMR/MSS in a 21-year-old man: a case report.Frontiers in oncology · 2025Article
- Immune Checkpoint Inhibitors Combined with Oncolytic Virotherapy: Synergy, Heterogeneity, and Safety in Cancer Treatment.Oncology research · 2025Review
- Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Epigenetics and immunotherapy in colorectal cancer: progress and promise.Clinical epigenetics · 2024Review
- Pan-cancer analysis of the transcriptional expression of histone acetylation enzymes in solid tumors defines a new classification scheme for gliomas.Frontiers in immunology · 2024Article
- Progresses in biomarkers for cancer immunotherapy.MedComm · 2023Review
- MHC Class II is Induced by IFNγ and Follows Three Distinct Patterns of Expression in Colorectal Cancer Organoids.Cancer research communications · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundApproximately 95% of advanced colorectal cancer patients (CRC) have mismatch repair MMR-proficient (MMRp) tumors, which do not respond to PD1 blockade alone. Preclinical studies have shown that combined histone deacetylases (HDAC) and/or DNA methyltransferases (DNMT) inhibition can induce susceptibility to immune checkpoint therapy and inhibit tumor growth. We conducted a pilot trial evaluating PD-1 immune checkpoint inhibitor therapy in combination with DNMT and HDAC inhibitors in MMRp CRC. The study was designed with a biological endpoint of change in immune cell infiltration, to determine the optimal epigenetic combination that optimizes the tumor microenvironment. This trial was designed to test that hypothesis.
resultsFrom January 2016 to November 2018, 27 patients were enrolled with median age of 57 (range 40-69) years. Median progression-free survival and overall survival were 2.79 months and 9.17, respectively. One patient in Arm C achieved a durable partial response by RECIST criteria, lasting for approximately 19 months. The most common treatment-related hematological adverse events in all arms were anemia (62%), lymphopenia (54%) and thrombocytopenia (35%), and non-hematological AEs were anorexia (65%), nausea (77%), and vomiting (73%).
conclusionsThe combination of 5-azacitidine and romidepsin with pembrolizumab was safe and tolerable in patients with advanced MMRp CRC, but with a minimal activity. Further mechanistic investigations are needed to understand epigenetic-induced immunologic shift and to expand the potential applicability of checkpoint inhibitors in this 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.