ArticleClinical epigenetics2015
Epigenetic synergy between decitabine and platinum derivatives.
Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- A phase 2 study of decitabine with or without carboplatin and arsenic trioxide in patients with MDS and AML.Blood neoplasia · 2025Trial
- Repurposing Azacitidine and Carboplatin to Prime Immune Checkpoint Blockade-resistant Melanoma for Anti-PD-L1 Rechallenge.Cancer research communications · 2022Trial
- Phase Ib/II study of safety and efficacy of low-dose decitabine-primed chemoimmunotherapy in patients with drug-resistant relapsed/refractory alimentary tract cancer.International journal of cancer · 2018Trial
- Trial
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- Azacitidine followed by R-GDP in transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma: preliminary results from a multicenter, phase II study.Therapeutic advances in hematology · 2025Article
- Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation.Clinical epigenetics · 2023Article
- Decitabine Treatment Induces a Viral Mimicry Response in Cervical Cancer Cells and Further Sensitizes Cells to Chemotherapy.International journal of molecular sciences · 2022Article
- PBRM1 Deficiency Sensitizes Renal Cancer Cells to DNMT Inhibitor 5-Fluoro-2'-Deoxycytidine.Frontiers in oncology · 2022Article
- The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications.Scientific reports · 2021Article
- Review
- Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy.Journal of clinical medicine · 2020Review
- Sequential decitabine and carboplatin treatment increases the DNA repair protein XPC, increases apoptosis and decreases proliferation in melanoma.BMC cancer · 2018Article
- Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy.Scientific reports · 2017Article
- DNA Hypomethylating Drugs in Cancer Therapy.Cold Spring Harbor perspectives in medicine · 2017Review
- Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications.International journal of radiation biology · 2017Review
- Repositioning FDA-Approved Drugs in Combination with Epigenetic Drugs to Reprogram Colon Cancer Epigenome.Molecular cancer therapeutics · 2017Article
- Transcriptional Selectivity of Epigenetic Therapy in Cancer.Cancer research · 2017Article
- Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.Chemical reviews · 2016Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAberrant epigenetic silencing of tumor suppressor genes has been recognized as a driving force in cancer. Epigenetic drugs such as the DNA methylation inhibitor decitabine reactivate genes and are effective in myeloid leukemia, but resistance often develops and efficacy in solid tumors is limited. To improve their clinical efficacy, we searched among approved anti-cancer drugs for an epigenetic synergistic combination with decitabine.
resultsWe used the YB5 cell line, a clonal derivative of the SW48 colon cancer cell line that contains a single copy of a hypermethylated cytomegalovirus (CMV) promoter driving green fluorescent protein (GFP) to screen for drug-induced gene reactivation and synergy with decitabine. None of the 16 anti-cancer drugs tested had effects on their own. However, in combination with decitabine, platinum compounds showed striking synergy in activating GFP. This was dose dependent, observed both in concurrent and sequential combinations, and also seen with other alkylating agents. Clinically achievable concentrations of carboplatin at (25 μM) and decitabine reactivated GFP in 28 % of the YB5 cells as compared to 15 % with decitabine alone. Epigenetic synergy was also seen at endogenously hypermethylated tumor suppressor genes such as MLH1 and PDLIM4. Genome-wide studies showed that reactivation of hypermethylated genes by the combination was significantly better than that induced by decitabine alone or carboplatin alone. Platinum compounds did not enhance decitabine-induced hypomethylation. Rather, we found significantly inhibited HP1α expression by carboplatin and the combination. This was accompanied by increased histone H3 lysine 4 (H3K4) trimethylation and histone H3 lysine 9 (H3K9) acetylation at reactivated genes (P < 0.0001) and reduced occupancy by methyl-binding proteins including MeCP2 and methyl-CpG-binding domain protein 2 (MBD2) (P < 0.0001).
conclusionsOur results suggest that the combination of decitabine with platinum analogs shows epigenetic synergy that might be exploited in the treatment of different cancers.
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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.