ArticleCancer research2015
KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- Review
- Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations.International journal of molecular sciences · 2024Article
- Mechanisms of Cell Death Induced by Erastin in Human Ovarian Tumor Cells.International journal of molecular sciences · 2024Article
- Alteration of DNA methyltransferases by eribulin elicits broad DNA methylation changes with potential therapeutic implications for triple-negative breast cancer.Epigenomics · 2024Article
- Genome-wide quantification of copy-number aberration impact on gene expression in ovarian high-grade serous carcinoma.BMC cancer · 2024Article
- Cancer epigenetics: from laboratory studies and clinical trials to precision medicine.Cell death discovery · 2024Review
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- DNA methylation profiles in cancer: functions, therapy, and beyond.Cancer biology & medicine · 2023Article
- DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in gastric cancer cells.Epigenetics · 2023Article
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- Pan-cancer molecular subtypes of metastasis reveal distinct and evolving transcriptional programs.Cell reports. Medicine · 2023Article
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
- DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation.Annals of medicine · 2022Review
- Double-stranded RNA induction asa potential dynamic biomarkerfor DNA-demethylating agents.Molecular therapy. Nucleic acids · 2022Article
- KITMolecular cancer therapeutics · 2021Article
- DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application.Clinical epigenetics · 2021Review
- Modulation of the Endothelin System in Colorectal Cancer Liver Metastasis: Influence of Epigenetic Mechanisms?Frontiers in pharmacology · 2020Article
- LINC00162 confers sensitivity to 5-Aza-2'-deoxycytidine via modulation of an RNA splicing protein, HNRNPH1.Oncogene · 2019Article
- Computational Analyses Connect Small-Molecule Sensitivity to Cellular Features Using Large Panels of Cancer Cell Lines.Methods in molecular biology (Clifton, N.J.) · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells. Pretreatment with decitabine decreased the cytotoxic activity of MEK inhibitors in KRAS-mutant ovarian cancer cells, with reciprocal downregulation of DNMT1 and MEK/ERK phosphorylation. In parallel with these responses, decitabine also upregulated the proapoptotic BCL-2 family member BNIP3, which is known to be regulated by MEK and ERK, and heightened the activity of proapoptotic small-molecule navitoclax, a BCL-2 family inhibitor. In a xenograft model of KRAS-mutant ovarian cancer, combining decitabine and navitoclax heightened antitumor activity beyond administration of either compound alone. Our results define the RAS/MEK/DNMT1 pathway as a determinant of sensitivity to DNA methyltransferase inhibition, specifically implicating KRAS status as a biomarker of drug response in ovarian cancer.
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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.