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Review Open Access

Virulence factors of the microbiome: A functional toolkit for cancer progression (Review)

  • Authors:
    • Kiruthika Vijayakumar
    • Benedict Christopher Paul
  • View Affiliations / Copyright

    Affiliations: Department of Biotechnology, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu 600116, India
    Copyright: © Vijayakumar et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 48
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    Published online on: May 11, 2026
       https://doi.org/10.3892/mco.2026.2957
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Abstract

The paradigm of cancer biology has shifted to recognize tumor as a complex ecosystem inhabited by a diverse microbiome. Beyond mere association, the molecular mechanisms driven by microbial virulence factors are critical for understanding how these microorganisms contribute to malignancy. The present review describes a virulence factor‑centric framework to deconstruct the microbial ‘toolkit’ and illustrate its role in enabling the Hallmarks of Cancer. The major classes of virulence factors were systematically analyzed, detailing how each contributes to tumor progression. It was described how bacterial adhesins (for example, Fusobacterium adhesin A and Fap2) initiate oncogenic signaling and mediate immune evasion; how secreted toxins drive genomic instability (Colibactin and CDT) and corrupt cellular signaling pathways (CagA and Bacteroides fragilis toxin); how degradative enzymes (gingipains and collagenases) dismantle the extracellular matrix to facilitate physical invasion; how viral oncoproteins (Human Papillomavirus E6/E7 and Epstein Barr virus latent membrane protein 1) hijack core cell cycle machinery; and how microbial structural components (lipopolysaccharides and extracellular vesicles) and metabolites (secondary bile acids) sustain a pro‑tumorigenic environment. This analysis reveals a pattern of functional convergence, where diverse microbial agents repeatedly target core host pathways such as NF‑κB, Wnt/β‑catenin and p53. This mechanistic understanding reframes the microbiome as an active orchestrator of malignancy and reveals a new frontier of therapeutic targets. Strategies aimed at neutralizing specific virulence factors or modulating the tumor ecosystem represent a novel and promising pillar in oncology.
View Figures

Figure 1

Microbial toolkit for cancer
progression. This schematic organizes the classic Hallmarks of
Cancer into three functional phases of progression: (blue),
(yellow), and (red). The model illustrates how specific
microorganisms exploit distinct virulence factors to drive these
cancer hallmarks. Representative microbes are paired with icons
indicating their primary class of virulence factor: Toxins,
adhesins, oncoproteins, degradative enzymes, and other metabolites.
The image was generated using Microsoft Copilot. LPS,
lipopolysaccharide.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Vijayakumar K and Paul BC: Virulence factors of the microbiome: A functional toolkit for cancer progression (Review). Mol Clin Oncol 25: 48, 2026.
APA
Vijayakumar, K., & Paul, B.C. (2026). Virulence factors of the microbiome: A functional toolkit for cancer progression (Review). Molecular and Clinical Oncology, 25, 48. https://doi.org/10.3892/mco.2026.2957
MLA
Vijayakumar, K., Paul, B. C."Virulence factors of the microbiome: A functional toolkit for cancer progression (Review)". Molecular and Clinical Oncology 25.1 (2026): 48.
Chicago
Vijayakumar, K., Paul, B. C."Virulence factors of the microbiome: A functional toolkit for cancer progression (Review)". Molecular and Clinical Oncology 25, no. 1 (2026): 48. https://doi.org/10.3892/mco.2026.2957
Copy and paste a formatted citation
x
Spandidos Publications style
Vijayakumar K and Paul BC: Virulence factors of the microbiome: A functional toolkit for cancer progression (Review). Mol Clin Oncol 25: 48, 2026.
APA
Vijayakumar, K., & Paul, B.C. (2026). Virulence factors of the microbiome: A functional toolkit for cancer progression (Review). Molecular and Clinical Oncology, 25, 48. https://doi.org/10.3892/mco.2026.2957
MLA
Vijayakumar, K., Paul, B. C."Virulence factors of the microbiome: A functional toolkit for cancer progression (Review)". Molecular and Clinical Oncology 25.1 (2026): 48.
Chicago
Vijayakumar, K., Paul, B. C."Virulence factors of the microbiome: A functional toolkit for cancer progression (Review)". Molecular and Clinical Oncology 25, no. 1 (2026): 48. https://doi.org/10.3892/mco.2026.2957
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