Evidence map›Paper›PMID 42809705›Full record

ArticleCancer research communications2026

Auranofin Potentiates Cisplatin Response in the Setting of Context-Dependent NOTCH-Associated Signaling States in Endometrial Cancer.

Robert J Lake, Cynthia Tshibangu, Niko J Candia, Quinn U Abfalterer, Irina V Lagutina, Christine Pauken, Kimberly K Leslie, Mara P Steinkamp, Hua-Ying Fan

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Robert J LakeProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0009-0001-7196-5710
Cynthia TshibanguProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0009-0003-2063-5177
Niko J CandiaProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0009-0009-9102-7439
Quinn U AbfaltererProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0000-0001-8456-5663
Irina V LagutinaAnimal Models Shared Resource, Comprehensive Cancer Center, University of New Mexico, Albuquerque, New Mexico.ORCID 0000-0001-9538-4008
Christine PaukenProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0009-0007-0748-1272
Kimberly K LeslieProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0000-0002-2704-8990
Mara P SteinkampProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0000-0003-1226-9325
Hua-Ying FanProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.ORCID 0000-0003-1790-4041

Funding

Center for Cancer Research (CCR) P30CA118100National Cancer Institute (NCI) 21CA286210National Cancer Institute (NCI) P50CA265793U.S. Department of War (DOW) CA210610U.S. Department of War (DOW) OC230061
6 · The paper itself

Abstract

Therapeutic resistance remains a major challenge in advanced and recurrent endometrial cancer. Aberrant NOTCH signaling has been associated with aggressive tumor behavior and therapeutic resistance across multiple malignancies, yet its therapeutic significance in endometrial cancer remains incompletely defined. We investigated whether auranofin (AuR), a pleiotropic gold-containing compound that inhibits thioredoxin reductase and can disrupt RBPJ chromatin occupancy, alters platinum responsiveness in endometrial cancer models. Upper-quartile NOTCH3 copy number was associated with poorer overall survival in The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma cohort, although this association was not retained with median-based stratification, continuous Cox proportional hazards modeling, or multivariable adjustment for clinicopathologic and molecular context. AuR treatment reduced RBPJ occupancy at canonical NOTCH target loci, including HES1 and HES4, across multiple endometrial cancer models, although this was not accompanied by significant changes in steady-state HES1 or HES4 transcript levels in AN3CA or ARK-1 cells. Stable NOTCH3 depletion produced context-dependent effects on AuR responsiveness and significantly enhanced cisplatin (CDDP) sensitivity in AN3CA cells. Pharmacologic AuR treatment similarly potentiated CDDP response in AN3CA cells and xenografts, resulting in reduced tumor burden and prolonged endpoint-free survival following combination treatment. In contrast, ARK-1 xenografts demonstrated limited additional benefit from combined AuR plus CDDP therapy despite detectable suppression of RBPJ occupancy. Together, these findings identify context-dependent NOTCH-associated therapeutic vulnerabilities in endometrial cancer and support further investigation of AuR-based platinum-sensitization strategies in biologically defined tumor contexts. SIGNIFICANCE: AuR disrupts RBPJ chromatin occupancy and enhances CDDP response in biologically distinct endometrial cancer contexts.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsAuranofinCisplatinEndometrial NeoplasmsReceptor, Notch3Receptors, NotchAnimalsCell Line, TumorDrug Resistance, NeoplasmDrug SynergismFemaleGene Expression Regulation, NeoplasticHumansMiceSignal TransductionXenograft Model Antitumor AssaysAuranofinCisplatinNOTCH3 protein, humanReceptor, Notch3Receptors, Notch

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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.