Evidence map›Paper›PMID 39506058›Full record

ArticleScientific reports2024

Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids.

Christoph Rogmans, Jan Dittrich, Emily Hamm, Jörg Paul Weimer, David Holthaus, Norbert Arnold, Inken Flörkemeier, Nicolai Maass, Peer Jansen, Astrid Dempfle and 2 more

Abstract read
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In one paragraph

Article in Scientific reports, 2024. 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

12 authors.

Christoph RogmansDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Jan DittrichDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Emily HammDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Jörg Paul WeimerDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
David HolthausDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Norbert ArnoldDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Inken FlörkemeierDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Nicolai MaassDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Peer JansenDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Astrid DempfleInstitute of Medical Informatics and Statistics, Kiel University and University Medical Center, Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Dirk O BauerschlagDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany.
Nina HedemannDepartment of Gynecology and Obstetrics, Kiel University and University Medical Center Schleswig-Holstein Campus Kiel, 24105, Kiel, Germany. nina.hedemann@uksh.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acquired or de novo resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) is a major challenge to ovarian cancer treatment. Therefore, strategies to overcome PARPi resistance are critical to improve prognosis. The purpose of this study is to evaluate whether inhibition of ADAM17 sensitizes ovarian cancer to treatment with olaparib, a PARPi, thereby bypassing resistance mechanisms and improving treatment response. Thus, we analyzed the effect of olaparib in combination with the ADAM17 inhibitor GW280264X in ovarian cancer using a 2D monolayer and a 3D spheroid model followed by a multicontent readout (viability, caspase activation and cytotoxicity). To emphasize the translational aspect of our work, we performed corresponding experiments on primary cells derived from ovarian cancer patients initially screened for their mutation status of the breast cancer gene (BRCA 1/2). In 2D, we observed a significant reduction in cell viability and a subsequent increase in apoptosis of the combined treatment (olaparib + GW280264X) compared with olaparib mono-treatment. The combined treatment allows a substantial dose reduction of olaparib rendering a strong synergistic effect. Using a 3D spheroid model from primary cells, we confirmed the 2D monoculture results and demonstrated not only increased caspase activity under the combined treatment but also a substantial gain in cytotoxicity compared to the mono-treatment. Our study proposes ADAM17 inhibition sensitizing ovarian cancer to olaparib treatment and improving treatment response.

Indexed as

ADAM17 ProteinOvarian NeoplasmsPhthalazinesPiperazinesSpheroids, CellularApoptosisCell Line, TumorCell SurvivalDrug Resistance, NeoplasmDrug SynergismFemaleHumansPoly(ADP-ribose) Polymerase InhibitorsTumor Cells, CulturedADAM17 ProteinADAM17 protein, humanolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase Inhibitors3D tumor spheroidsADAM17OlaparibOvarian cancerPARP-inhibitorResistance

Identifiers

PMID39506058
PMCPMC11541916

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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.