Evidence mapPaperPMID 41749816Full record

ArticleCancers2026

Personalized Combination Therapy in Bladder Cancer: cAMP Modulators Synergize with 5-FU and Modulate Redox Programs.

Eduarda Ribeiro, Nuno Vale

Abstract read
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

  1. Review
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4 · The record

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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

2 authors.

Eduarda RibeiroPerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.ORCID 0009-0009-5370-9586
Nuno ValePerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.ORCID 0000-0002-1283-1042

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesRepurposed cAMP-elevating agents may personalize fluoropyrimidine therapy by exploiting pathway-specific vulnerabilities.

methodsWe tested the PDE3 inhibitor milrinone and the β2-agonist terbutaline alone or combined with 10 μM 5-fluorouracil (5-FU) in UM-UC-5 (bladder), A549 (lung), and PC-3 (prostate) cells. Viability, migration, clonogenicity, and intracellular ROS (DCFDA) were measured; drug interactions used Chou-Talalay/CompuSyn.

resultsIn UM-UC-5, both agents reduced viability, migration, and clonogenicity and synergized with 5-FU (CI < 1 across Fa ≈ 0.42-0.57). 5-FU increased ROS, whereas terbutaline consistently lowered ROS below baseline and blunted 5-FU-induced oxidative signals; milrinone showed a dose-dependent redox profile without consistent ROS suppression. A549 combinations did not outperform 5-FU; PC-3 was largely unresponsive.

conclusionscAMP modulators selectively potentiate 5-FU in bladder cancer cells and modulate redox programs (notably with terbutaline), supporting a biomarker-guided combination strategy (e.g., β2-AR/PDE3/PI3K-Akt features) for personalized therapy in bladder cancer; mechanistic and in vivo validation are warranted.

Indexed as

5-fluorouracilbiomarker-guided therapybladder cancercAMP modulatorscombination indexdrug repurposingPDE3 inhibitorpersonalized medicineredox programsβ2-adrenergic agonist

Identifiers

PMID41749816
PMCPMC12938384

What Socratic holds

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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.