Evidence mapPaperPMID 40925231Full record

ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2025

Molecular impact of NOTCH signaling dysregulation on ovarian cancer progression, chemoresistance, and taxane response.

Kamila Koucka, Alzbeta Spalenkova, Karolina Seborova, Tereza Tesarova, Marie Ehrlichova, Ivona Krus, Petr Holy, Lukas Rob, Martin Hruda, Jiri Bouda and 9 more

Abstract read
In one paragraph

Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 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

19 authors.

Kamila KouckaToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Alzbeta SpalenkovaToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Karolina SeborovaToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Tereza TesarovaToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Marie EhrlichovaToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Ivona KrusToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Petr HolyToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Lukas RobDepartment of Gynecology and Obstetrics, Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
Martin HrudaDepartment of Gynecology and Obstetrics, Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic.
Jiri BoudaDepartment of Gynecology and Obstetrics, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
Alena BartakovaDepartment of Gynecology and Obstetrics, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
Vendula SmoligovaDepartment of Gynecology and Obstetrics, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
Iwao OjimaInstitute of Chemical Biology & Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY, United States.
Lei ChenInstitute of Chemical Biology & Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY, United States.
Hersch BendaleInstitute of Chemical Biology & Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY, United States.
Marcela MrhalovaDepartment of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Katerina KopeckovaDepartment of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Pavel SoucekToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Radka VaclavikovaToxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. Electronic address: radka.vaclavikova@szu.gov.cz.

Funding

Taxane and Taxoid Chemotherapeutic AgentsR01CA103314 · STATE UNIVERSITY NEW YORK STONY BROOK · 2003 to 2005
$968k
NCI NIH HHS R01 CA103314
6 · The paper itself

Abstract

Patients with epithelial ovarian cancer (EOC) face high mortality due to late diagnosis, recurrence, metastasis, and drug resistance. The NOTCH signaling pathway plays a critical role in cancer progression. This study analyzed NOTCH pathway deregulation in EOC patients and its response to taxane treatment in vitro and in vivo. In tumor cells of EOC patients, a significant upregulation of NOTCH1/3/4 and JAG2 and a downregulation of the NOTCH2 gene were found. The observed high levels of NOTCH3 mRNA were also confirmed at the protein level. In contrast, we observed a significant association of low NOTCH4 expression with the presence of peritoneal metastasis and shortened platinum-free interval. In the resistant in vitro cell line model, significant upregulation of NOTCH signaling pathway, namely NOTCH3, was observed after treatment with experimental Stony Brook taxanes (SB-Ts), with high efficacy against paclitaxel-resistant ovarian tumor cells. The administration of SB-Ts also caused NOTCH3 upregulation in an effective combination regimen with paclitaxel in comparison to paclitaxel alone and untreated control in the in vivo cell-derived xenograft mouse model of resistant ovarian cancer. Knockdown of the NOTCH3 gene caused higher sensitivity of resistant cells to taxanes, suggesting that NOTCH3-specific inhibition may potentially bring therapeutic benefits in resistant ovarian carcinoma. Based on our results, we suggest the NOTCH3 gene as a potential target for preclinical studies on resistant ovarian tumors. The current study also highlights the NOTCH4 gene as a potential predictive biomarker of therapeutic response in ovarian cancer.

Indexed as

Carcinoma, Ovarian EpithelialDrug Resistance, NeoplasmOvarian NeoplasmsReceptors, NotchSignal TransductionTaxoidsAnimalsBridged-Ring CompoundsCell Line, TumorDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeMiddle AgedBridged-Ring CompoundsNOTCH3 protein, humanPaclitaxelReceptor, Notch3Receptors, NotchtaxaneTaxoidschemoresistancedysregulationNOTCH signaling pathwayovarian cancerprognosistaxanes

Identifiers

PMID40925231
PMCPMC12499955

What Socratic holds

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Registered trials

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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 Socratic graph.