Microbial Genotoxins as Emerging Drivers of Cancer: Mechanisms, Detection, and Therapeutic Opportunities

Through DNA damage, disruption of repair pathways, and chronic inflammation, microbial genotoxins found in bacteria, viruses, fungi, and parasites are important causes of cancer. Their taxonomic diversity, molecular mechanisms, and functions in forming mutational signatures linked to cancer are summarized in this review. Fungal aflatoxins, viral proteins like HPV E6/E7, and bacterial genotoxins like colibactin and cytolethal distending toxin cause unique DNA lesions, such as double-strand breaks and adducts, that lead to oncogenic changes. These genotoxins create pro-carcinogenic microenvironments by enhancing oxidative stress, disrupting DNA repair, and dysregulating cell cycle checkpoints. Genotoxin signatures can be precisely identified thanks to advanced detection techniques like proteomics, whole-genome sequencing, and genotoxicity assays. Promising interventions include DNA repair enhancement therapies and preventive measures like vaccination, microbiome modification, and toxin inhibitors. The review promotes public health measures to lower genotoxin exposure and emphasizes translational implications for precision oncology, such as early detection and risk stratification. To mitigate genotoxin-driven cancers, interdisciplinary research is necessary to bridge knowledge gaps, such as establishing causation in human cohorts and developing long-term infection models.