Evidence map›Paper›PMID 40985842›Full record

ArticleCancer research communications2025

Auranofin Synergizes with Cisplatin in Reducing Tumor Burden of NOTCH-Dependent Ovarian Cancer.

Robert J Lake, Parisa Nikeghbal, Irina V Lagutina, Kimberly K Leslie, Mara P Steinkamp, Hua-Ying Fan

Abstract read
In one paragraph

Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

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.

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

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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

6 authors.

Robert J LakeProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science Center, Albuquerque, New Mexico.ORCID 0009-0001-7196-5710
Parisa NikeghbalBiomedical Sciences Graduate Program, University of New Mexico Health Science Center, Albuquerque, New Mexico.ORCID 0000-0002-6954-7544
Irina V LagutinaAnimal Models Shared Resource, Comprehensive Cancer Center, University of New Mexico, Albuquerque, New Mexico.ORCID 0000-0001-9538-4008
Kimberly K LeslieProgram in Cell and Molecular Oncology, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Science 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 Science 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 Science Center, Albuquerque, New Mexico.ORCID 0000-0003-1790-4041

Funding

WOMEN'S CANCERS RESEARCH PROGRAMP30CA118100 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Yolanda Sanchez · 2005 to 2026
$57.1M
Targeted Therapy for Endometrial CancerR01CA099908 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI LESLIE, KIMBERLY K. · 2002 to 2023
$5.8M
Repurposing Auranofin As a Novel Notch Pathway Inhibitor for Combinational Ovarian Cancer TherapyR21CA286210 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI FAN, HUA-YING · 2024 to 2025
$392k
Optimal DNA Brain-Penetrating Nanoparticle (DNA-BPN) Formulation for Glioblastoma (GBM) TreatmentF31CA210610 · NCI · JOHNS HOPKINS UNIVERSITY · PI NEGRON, KARINA · 2016 to 2018
$125k
Center for Cancer Research (CCR) P30CA118100National Cancer Institute (NCI) CA210610National Cancer Institute (NCI) R01 5CA99908-22National Cancer Institute (NCI) R21CA286210NCI NIH HHS F31 CA210610NCI NIH HHS P30 CA118100NCI NIH HHS R01 CA099908NCI NIH HHS R21 CA286210Ovarian Cancer Academy (DODOCA) OC230061
6 · The paper itself

Abstract

The NOTCH pathway regulates cell proliferation, differentiation, and stem cell maintenance. Thus, aberrant NOTCH activation plays a key role in cancer initiation, progression, and chemoresistance. Mutations and amplification of NOTCH pathway genes have been identified in high-grade serous ovarian cancers and are associated with poor clinical outcomes. Among the four NOTCH receptors, NOTCH3 alterations were strongly correlated with poor overall survival. Previously, we identified auranofin, an oral gold salt therapeutic compound, as a novel NOTCH pathway inhibitor that disrupts the DNA binding of RBPJ, the major downstream transcriptional effector of the NOTCH pathway. In this study, we surveyed the response of eight ovarian cancer cell lines to auranofin and found IC50 values ranging from 1.7 to 12 μmol/L, with NOTCH3-negative SKOV3 cells having the highest IC50 value. In NOTCH-dependent OVCAR3 cells, auranofin synergized with cisplatin to enhance cell death. Importantly, auranofin treatment led to a dose-dependent decrease in RBPJ occupancy at the NOTCH-dependent promoters, HES1 and HES4. Furthermore, knocking down NOTCH3 in OVCAR3 cells significantly decreased sensitivity to auranofin, further supporting the notion that NOTCH3 signaling is a major target of auranofin. Moreover, auranofin increased cisplatin efficacy in an OVCAR3-derived xenograft mouse model. Using eight patient-derived cancer organoid models, we found that auranofin increased cisplatin efficacy in killing cancer organoids generated from clinically platinum-sensitive patients but also restored platinum response in a subset of organoid models developed from platinum-resistant patients. These studies underscore the potential of auranofin to improve platinum-based cancer therapy, particularly in NOTCH3-expressing cancers. SIGNIFICANCE: NOTCH signaling underlies cancer initiation, progression, and chemoresistance. Our study revealed the potential of auranofin as a NOTCH pathway inhibitor to enhance the efficacy of platinum-based ovarian cancer therapy.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsAuranofinCisplatinOvarian NeoplasmsReceptors, NotchAnimalsCell Line, TumorCell ProliferationDrug SynergismFemaleHumansImmunoglobulin J Recombination Signal Sequence-Binding ProteinMiceReceptor, Notch3Signal TransductionTumor BurdenAuranofinCisplatinImmunoglobulin J Recombination Signal Sequence-Binding ProteinNOTCH3 protein, humanRBPJ protein, humanReceptor, Notch3Receptors, Notch

Identifiers

PMID40985842
PMCPMC12512110

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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.