Growing evidence from multi-cancer cohort studies has positioned the oral pathobiont Fusobacterium nucleatum (F. nucleatum) as an emerging microbial contributor to cancer progression. Increased intratumoral abundance of F. nucleatum has been reported in colorectal, breast, esophageal, pancreatic, oral, and gastric cancers and is frequently associated with adverse clinicopathological features, treatment resistance, metastatic behavior, and poor prognosis. Advances in microbiome profiling, spatial analysis, and single-cell technologies have begun to reveal how F. nucleatum colonizes tumors and interacts with host cells and tumor-associated microbial communities. This review summarizes current evidence regarding the tumor-associated activities of F. nucleatum, with emphasis on its routes of tumor entry, spatiotemporal colonization patterns, adhesion- and glycan-dependent tropism, polymicrobial niche formation, and crosstalk with cancer cells and immune components.
We discuss how F. nucleatum promotes oncogenic signaling, inflammatory amplification, genomic and epigenetic reprogramming, epithelial-mesenchymal transition, metastatic dissemination, immune evasion, and therapy adaptation. Particular attention is given to its context-dependent effects on chemotherapy, radiotherapy, and immunotherapy responses, as well as emerging strategies aimed at detecting or selectively targeting intratumoral F. nucleatum. F. nucleatum represents both a biomarker-associated organism and a potentially modifiable component of the tumor microenvironment. Defining its strain-level heterogeneity, spatial ecology, and therapy-specific functions will be essential for translating microbiome-guided precision oncology from mechanistic insight into clinical application.
F. nucleatum colonises tumours through mucosal translocation, adjacent-tissue migration and hematogenous dissemination. It promotes cancer progression via adhesion, inflammation, immune evasion, epigenetic remodelling and metastasis. Its effects on therapy response are tumour-context dependent. Microbiome-guided targeting may enable precision oncology.
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