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

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.