Evidence mapPaperPMID 39550583Full record

ArticleCancer cell international2024

Integrated proteomics and metabolomics analyses reveal new insights into the antitumor effects of valproic acid plus simvastatin combination in a prostate cancer xenograft model associated with downmodulation of YAP/TAZ signaling.

Federica Iannelli, Rita Lombardi, Susan Costantini, Maria Serena Roca, Laura Addi, Francesca Bruzzese, Elena Di Gennaro, Alfredo Budillon, Biagio Pucci

Abstract read
In one paragraph

Article in Cancer cell international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Role ofMicroorganisms · 2025
    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

9 authors.

Federica Iannelli *Experimental Pharmacology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Rita Lombardi *Experimental Animal Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Susan CostantiniExperimental Pharmacology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Maria Serena RocaExperimental Pharmacology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Laura AddiExperimental Pharmacology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Francesca BruzzeseExperimental Animal Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Elena Di GennaroExperimental Pharmacology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.
Alfredo BudillonScientific Directorate, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Via M. Semmola, Napoli, 80131, Italy. a.budillon@istitutotumori.na.it.
Biagio PucciExperimental Pharmacology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, 80131, Italy.

Funding

Ministero della Salute Ricerca Corrente Funds - Linea 2/2 to ABRegione Campania POR FESR 2014/2020 Progetto Campania Onco-Terapie/CUP: B61G18000470007
6 · The paper itself

Abstract

backgroundDespite advancements in therapeutic approaches, including taxane-based chemotherapy and androgen receptor-targeting agents, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable tumor, highlighting the need for novel strategies that can target the complexities of this disease and bypass the development of drug resistance mechanisms. We previously demonstrated the synergistic antitumor interaction of valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitory activity, with the lipid-lowering drug simvastatin (SIM). This combination sensitizes mCRPC cells to docetaxel treatment both in vitro and in vivo by targeting the cancer stem cell compartment via mevalonate pathway/YAP axis modulation.

methodsHere, using a combined proteomic and metabolomic/lipidomic approach, we characterized tumor samples derived from 22Rv1 mCRPC cell-xenografted mice treated with or without VPA/SIM and performed an in-depth bioinformatics analysis.

resultsWe confirmed the specific impact of VPA/SIM on the Hippo-YAP signaling pathway, which is functionally related to the modulation of cancer-related extracellular matrix biology and metabolic reprogramming, providing further insights into the molecular mechanism of the antitumor effects of VPA/SIM.

conclusionsIn this study, we present an in-depth exploration of the potential to repurpose two generic, safe drugs for mCRPC treatment, valproic acid (VPA) and simvastatin (SIM), which already show antitumor efficacy in combination, primarily affecting the cancer stem cell compartment via MVP/YAP axis modulation. Bioinformatics analysis of the LC‒MS/MS and

Indexed as

Drug repurposingMetabolomicsProstate cancerProteomicsSimvastatinValproic acid

Identifiers

PMID39550583
PMCPMC11569608

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.