Targeting Fusobacterium nucleatum in cancer therapy: A new frontier in solid tumor treatment.

Recently, the tumor-infiltrating microbiome (TIM) has gained increasing attention due to its pivotal role in carcinogenesis, tumor progression, resistance to chemotherapy, and immune evasion. Although the composition of these microbial communities is not yet fully elucidated, emerging studies have demonstrated that certain bacteria exert pro-tumoral effects, either through enzymatic activities or by modulating the host immune response. Among them, Fusobacterium nucleatum (Fn) represents one of the most pathogenic residents of several solid tumors, making it a novel and promising target in the fight against cancer. In detail, Fn promotes oncogenic signaling, epithelial-mesenchymal transition, inflammatory responses, and autophagy-mediated drug resistance, thereby contributing to poor clinical outcomes. This review explores different strategies to selectively target Fn, aiming to reduce its pro-tumoral behavior, spanning from drug repurposing, synthetic small molecules, natural products, and antimicrobial peptides to advanced nanoformulations, vaccine-based platforms, and sequence-specific interventions, such as antisense oligomers and microbiota-modulating strategies. A focused section covers stimuli-responsive and biomimetic nanoplatforms potentially capable of eradicating Fn and restoring chemosensitivity, while sparing the commensal gut microbiota. Collectively, these findings support the feasibility of targeting the TIM in combination with canonical anticancer regimens. Although further refinements and additional investigations are needed, targeting Fn represents a novel paradigm shift in the management of bacterially colonized solid tumors.