Evidence map›Paper›PMID 42361323›Full record

ArticleCancer research communications2026

DNA Methyltransferase Inhibition Prevents Platinum-Induced Ovarian Cancer Stem Cell Enrichment.

Truc T Vuong, Riddhi Sood, Shu Zhang, Tara X Metcalfe, Rena Y Han, Kenneth P Nephew, Heather M O'Hagan

Abstract read
In one paragraph

Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Truc T VuongCell, Molecular and Cancer Biology Graduate Program, Indiana University School of Medicine, Bloomington, Indiana.ORCID 0009-0001-2088-2181
Riddhi SoodGenome, Cell and Developmental Biology, Department of Biology, Indiana University Bloomington, Bloomington, Indiana.ORCID 0000-0002-3274-0164
Shu ZhangIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana.ORCID 0000-0002-3442-4309
Tara X MetcalfeCell, Molecular and Cancer Biology Graduate Program, Indiana University School of Medicine, Bloomington, Indiana.ORCID 0000-0003-2074-9484
Rena Y HanMedical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana.ORCID 0009-0004-9551-1272
Kenneth P NephewCell, Molecular and Cancer Biology Graduate Program, Indiana University School of Medicine, Bloomington, Indiana.ORCID 0000-0003-2192-1346
Heather M O'HaganCell, Molecular and Cancer Biology Graduate Program, Indiana University School of Medicine, Bloomington, Indiana.ORCID 0000-0001-9750-5088

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI David W Clapp · 1999 to 2026
$59.3M
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Congressionally Directed Medical Research Programs (CDMRP) OC200099National Cancer Institute (NCI) P30CA082709-25National Center for Advancing Translational Sciences (NCATS) UL1TR002529NCATS NIH HHS UL1 TR002529NCI NIH HHS P30 CA082709Ovarian Cancer Alliance of Greater Cincinnati
6 · The paper itself

Abstract

Platinum-based therapy is the standard first-line treatment for high-grade serous ovarian cancer (HGSC). However, most patients develop resistance and recurrence despite an initial response to therapy. Ovarian cancer stem cells (OCSC) are enriched in recurrent tumors and contribute to platinum resistance. These tumors also show promoter DNA hypermethylation, and DNA methyltransferase inhibitors (DNMTi) have been shown to restore sensitivity in platinum-resistant ovarian cancer cells. In this study, we demonstrated that combining DNMTi treamtent with platinum prevented the platinum-induced enrichment of OCSCs and identified nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways as potential regulators of platinum-induced OCSC enrichment. STAT3 was active at baseline in ovarian cancer cells, and platinum treatment alone activated NF-κB while maintaining STAT3 activity. Platinum combined with DNMTi treatment decreased STAT3 activation, while still inducing NF-κB activation. Knockdown experiments demonstrated that the presence of both NF-κB and STAT3 was necessary for platinum-induced OCSC enrichment. Analysis of STAT3 and NF-κB subunit p65 CUT&RUN data showed increased binding in introns and intergenic regions in response to platinum. Additionally, DNMTi treatment enriched NF-κB binding at endogenous retroviruses, which correlated with changes in expression of nearby genes when DNMTi treatment was combined with platinum. We conclude that combining DNMTis with platinum modulates STAT3 and NF-κB activation and genomic binding, potentially influencing target gene expression and preventing platinum-induced enrichment of OCSCs. SIGNIFICANCE: OCSCs promote relapse and chemoresistance in HGSC. We show that combining standard platinum-based therapy with DNMTi treatment prevents platinum-induced enrichment of OCSCs. Our findings support the use of DNMTis in combination with platinum as a strategy to reduce OCSC enrichment and platinum resistance in ovarian cancer.

Indexed as

Enzyme InhibitorsNeoplastic Stem CellsOvarian NeoplasmsPlatinumCell Line, TumorDNA MethylationDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansNF-kappa BSignal TransductionSTAT3 Transcription FactorEnzyme InhibitorsNF-kappa BPlatinumSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID42361323
PMCPMC13381740

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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.