Dietary Terpenoids in Advancing Biofilm-Mediated Cancer Prevention: Antibiofilm Cascade, Molecular Crosstalk, and Nano-Facilitated Functional Delivery.

The role of microbes in cancer is gaining attention these days, especially in the context of tumor-associated biofilms and dysbiotic microbiota. Biofilm-producing microorganisms, such as Fusobacterium nucleatum and Helicobacter pylori, trigger oncogenic inflammation and immune evasion in tumor initiation and progression, and in the development of chemoresistance, through the activation of the NF-κB, STAT3, and β-catenin pathways. Dietary terpenoids are a structurally diverse group of antitumor and antibiofilm plant metabolites. Monoterpenoids, sesquiterpenoids, and triterpenoids are known to inhibit quorum sensing, the biosynthesis of extracellular polymeric substances (EPS), and the expression of biofilm-associated virulence factors, proposing an unexplored convergence among antibiofilm and anticancer mechanisms. Importantly, the biofilm structure (thickness, developmental stage, EPS density) affects the efficacy of terpenoids, affecting diffusion, microbial persistence, and therapeutic susceptibility. The quorum-sensing disruption is more effective in the early stages of biofilms, while high concentrations of EPS in mature, thick biofilms will require more penetration to disrupt quorum sensing. Innovative functional food matrices, including nano-enabled delivery systems, are emerging strategies to improve bioavailability and microbiome modulation of terpenoids. Furthermore, nano-formulations allow better penetration in dense biofilm matrices, protect terpenoids from early degradation, and allow prolonged and focused drug release in the tumor microenvironment associated with biofilms. Combining precision nutrition with microbiome-informed dietary strategies can be used to prevent and treat cancer. The present review combines studies linking biofilm-driven carcinogenesis with terpenoid-mediated antibiofilm-anticancer pathways and nano-mediated functional delivery and biofilm penetration, including highlighting the potential for microbiome modulation in cancer therapy.