Evidence map›Paper›PMID 41216708›Full record

ArticleMolecular oncology2026

Improving PARP inhibitor efficacy in bladder cancer without genetic BRCAness by combination with PLX51107.

Jutta Schmitz, Anna L Bartkowiak, Michael Rose, Nora Kolks, Patrick Petzsch, Vandana Solanki, Anne Stoffel, Bianca Faßbender, Leandra Lepping, Julka Volkamer and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

16 authors.

Jutta SchmitzDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.
Anna L BartkowiakDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.
Michael RoseCenter for Integrated Oncology (CIO) Duesseldorf, CIO Aachen Bonn Cologne Duesseldorf, Germany.ORCID 0000-0002-4340-1117
Nora KolksDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.
Patrick PetzschGenomics and Transcriptomics Laboratory (GTL), Biological and Medical Research Center (BMFZ), Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.ORCID 0000-0002-8355-5524
Vandana SolankiDepartment of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, The Netherlands.
Anne StoffelDepartment of Haematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Germany.
Bianca FaßbenderDepartment of Haematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Germany.
Leandra LeppingDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.
Julka VolkamerDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.
Karl KöhrerGenomics and Transcriptomics Laboratory (GTL), Biological and Medical Research Center (BMFZ), Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.
Marc SeifertDepartment of Haematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Germany.
Tokameh MahmoudiDepartment of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, The Netherlands.
Tahlita C M ZuiverloonDepartment of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, The Netherlands.
Günter NiegischDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.ORCID 0000-0001-6929-8691
Michèle J HoffmannDepartment of Urology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Germany.ORCID 0000-0002-6044-1671

Funding

Wilhelm Sander-Stiftung 2022.071.1; 2022.071.2
6 · The paper itself

Abstract

Advanced urothelial carcinoma (UC) requires new therapeutics beyond chemo- and immunotherapies. Clinical trials with PARP inhibitors (PARPi), particularly in Cisplatin-treated UC, yielded limited response. Biomarker-based patient selection (apart from BRCAness) or combination treatment may increase efficacy. To identify the most suitable PARPi for UC, we compared Olaparib with Talazoparib. RNA sequencing of PARPi-treated UC lines revealed few common targets and a different impact on immune response. By analysis of experimental and public clinical data, we identified new UC-specific PARPi response predictors SLFN5, SLFN11, and OAS1. We investigated a new combination treatment using PLX51107, an epigenetic BET protein inhibitor, to increase PARPi efficacy. The Talazoparib + PLX51107 combination had a strong synergistic impact on UC cells and organoids, including Cisplatin-resistant cells, allowing dose reduction to spare benign cells. Mechanisms of synergism targeted homologous recombination repair, DNA replication, and apoptosis regulation. In conclusion, we suggest Talazoparib treatment of UC to be highly efficacious on all models examined when combined with PLX51107. This new combination treatment allows efficient application of PARPi Talazoparib to all UC patients, independent of Cisplatin pretreatment and genetic BRCAness.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsPhthalazinesPoly(ADP-ribose) Polymerase InhibitorsUrinary Bladder NeoplasmsCell Line, TumorDrug SynergismHumansPiperazinesolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorstalazoparibBET inhibitorbiomarkerBladder cancercombination therapyepigeneticsPARP inhibitor

Identifiers

PMID41216708
PMCPMC13042512

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.