Evidence map›Paper›PMID 36765842›Full record

ArticleCancers2023

Cerivastatin Synergizes with Trametinib and Enhances Its Efficacy in the Therapy of Uveal Melanoma.

Adriana Agnese Amaro, Rosaria Gangemi, Laura Emionite, Patrizio Castagnola, Gilberto Filaci, Martine J Jager, Enrica Teresa Tanda, Francesco Spagnolo, Matteo Mascherini, Ulrich Pfeffer and 1 more

Abstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. The Hippo signalling pathway and its impact on eye diseases.Journal of cellular and molecular medicine · 2024
    Pooled it
  2. Article
  3. Article
  4. Assessing Determinants of Response to PARP Inhibition in GermlineInternational journal of molecular sciences · 2025
    Article
  5. Review
  6. Article
  7. Article
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

11 authors.

Adriana Agnese AmaroIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0002-1573-7756
Rosaria GangemiIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
Laura EmioniteIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0002-5199-6384
Patrizio CastagnolaIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0003-2008-9199
Gilberto FilaciIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0001-6445-8414
Martine J JagerLeiden University Medical Center, 2333 ZA Leiden, The Netherlands.ORCID 0000-0003-2261-3820
Enrica Teresa TandaIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
Francesco SpagnoloIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
Matteo MascheriniIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.
Ulrich PfefferIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0003-0872-4671
Michela CroceIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0003-4683-4951

Funding

Alleanza Contro il Cancro progetto di Rete ACC 2021Compagnia di San Paolo 20067Ministero della Salute 5x1000 2016Ministero della Salute RC 2018-19Ministero della Salute RC 2022
6 · The paper itself

Abstract

backgroundMetastatic uveal melanoma (MUM) is a highly aggressive, therapy-resistant disease. Driver mutations in Gα-proteins GNAQ and GNA11 activate MAP-kinase and YAP/TAZ pathways of oncogenic signalling. MAP-kinase and MEK-inhibitors do not significantly block MUM progression, likely due to persisting YAP/TAZ signalling. Statins inhibit YAP/TAZ activation by blocking the mevalonate pathway, geranyl-geranylation, and subcellular localisation of the Rho-GTPase. We investigated drugs that affect the YAP/TAZ pathway, valproic acid, verteporfin and statins, in combination with MEK-inhibitor trametinib.

methodsWe established IC50 values of the individual drugs and monitored the effects of their combinations in terms of proliferation. We selected trametinib and cerivastatin for evaluation of cell cycle and apoptosis. Synergism was detected using isobologram and Chou-Talalay analyses. The most synergistic combination was tested in vivo.

resultsSynergistic concentrations of trametinib and cerivastatin induced a massive arrest of proliferation and cell cycle and enhanced apoptosis, particularly in the monosomic,

conclusionStatins can potentiate the efficacy of MEK inhibitors in the therapy of UM.

Indexed as

MEK inhibitorstatinsuveal melanomaYAP/TAZ

Identifiers

PMID36765842
PMCPMC9913575

What OpenQuestion 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 OpenQuestion graph.