Evidence map›Paper›PMID 38475767›Full record

ArticleJournal of translational medicine2024

Bacterial DnaK reduces the activity of anti-cancer drugs cisplatin and 5FU.

Francesca Benedetti, Emmanuel F Mongodin, Jonathan H Badger, Arshi Munawwar, Ashley Cellini, Weirong Yuan, Giovannino Silvestri, Carl N Kraus, Simone Marini, Chozha V Rathinam and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2024. 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
1.9field-weighted citation impact, top 17% of its field
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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. 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

14 authors at 4 institutions in 2 countries.

Francesca Benedetti *Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Emmanuel F Mongodin *Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Jonathan H BadgerLaboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA.
Arshi MunawwarInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Ashley CelliniPathology Biorepository Shared Service, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, 21201, USA.
Weirong YuanInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Giovannino SilvestriInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Carl N KrausAquestive, Warren, NJ, USA.
Simone MariniEmerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
Chozha V RathinamInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Marco SalemiEmerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
Hervé TettelinDepartment of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Robert C GalloInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. rgallo@ihv.umaryland.edu.
Davide ZellaInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. dzella@ihv.umaryland.edu.ORCID 0000-0001-5576-5770
University of Maryland, Baltimore · USUniversity of Florida · USAquestive (United States) · USUnited States Department of Health and Human Services · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChemotherapy is a primary treatment for cancer, but its efficacy is often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found that Mycoplasma fermentans DnaK, a chaperone protein, impairs p53 activities, which are essential for most anti-cancer chemotherapeutic responses.

methodsTo investigate the role of DnaK in chemotherapy, we treated cancer cell lines with M. fermentans DnaK and then with commonly used p53-dependent anti-cancer drugs (cisplatin and 5FU). We evaluated the cells' survival in the presence or absence of a DnaK-binding peptide (ARV-1502). We also validated our findings using primary tumor cells from a novel DnaK knock-in mouse model. To provide a broader context for the clinical significance of these findings, we investigated human primary cancer sequencing datasets from The Cancer Genome Atlas (TCGA). We identified F. nucleatum as a CAB carrying DnaK with an amino acid composition highly similar to M. fermentans DnaK. Therefore, we investigated the effect of F. nucleatum DnaK on the anti-cancer activity of cisplatin and 5FU.

resultsOur results show that both M. fermentans and F. nucleatum DnaKs reduce the effectiveness of cisplatin and 5FU. However, the use of ARV-1502 effectively restored the drugs' anti-cancer efficacy.

conclusionsOur findings offer a practical framework for designing and implementing novel personalized anti-cancer strategies by targeting specific bacterial DnaKs in patients with poor response to chemotherapy, underscoring the potential for microbiome-based personalized cancer therapies.

Indexed as

Antineoplastic AgentsNeoplasmsAnimalsBacteriaCisplatinFluorouracilHumansMiceTumor Suppressor Protein p53Antineoplastic AgentsCisplatinFluorouracilTumor Suppressor Protein p535FUAnti-cancer therapyCisplatinDnaKFusobacteriumMycoplasmap53TCGA

Identifiers

PMID38475767
PMCPMC10935962
OpenAlexW4392695871

What Socratic holds

Textmetadata
LicenceCC BY
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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.