Fusobacterium nucleatum mediated crosstalk drives cisplatin resistance in head and neck cancer

Cisplatin remains a cornerstone of head and neck cancer (HNC) treatment, yet resistance frequently undermines therapeutic efficacy. Emerging evidence implicates Fusobacterium nucleatum, enriched in the tumour microbiome, in promoting chemoresistance via molecular and microenvironmental mechanisms. This review synthesises evidence from PubMed, Scopus, and Web of Science (January 2015-September 2025) examining F. nucleatum’s contribution to cisplatin resistance in HNC. Cisplatin resistance involves tumour-intrinsic pathways, such as nucleotide excision repair, homologous recombination, and ATP7B-mediated drug efflux. F. nucleatum indirectly enhances resistance via Wnt5a/Ca²⁺–NFATc3 signalling, downregulation of p53 and E-cadherin, and activation of the NLRP3 inflammasome, which recruits myeloid-derived suppressor cells. It also amplifies inflammation and chemoresistance by escalating the senescence-associated secretory phenotype, promoting a tumour-supportive microenvironment. These findings highlight microbiome host crosstalk as a therapeutic target, suggesting that microbiota-directed strategies alongside cisplatin may improve outcomes in resistant HNC.