Stage-Specific carcinogenic mechanisms and intervention strategies for pks+ Escherichia coli-associated colorectal cancer.

Colorectal cancer (CRC) incidence is increasing in many regions, particularly among individuals younger than 50 years. The gut microbiota has emerged as an important regulator of CRC development and treatment response. Among microbial factors, Escherichia coli (E. coli) strains harboring the polyketide synthase (pks) gene island are of particular interest because they produce the genotoxin colibactin. Colibactin induces DNA damage and characteristic mutational signatures, suggesting a potential role in CRC evolution. Rather than acting as a single carcinogenic factor, pks⁺ E. coli-associated carcinogenesis can be viewed as a host-microbe interaction-driven, multistage process involving bacterial colonization, colibactin biosynthesis, DNA damage, mutation accumulation, cellular fate remodeling, microenvironmental amplification, host susceptibility, and clonal expansion. This review summarizes stage-specific intervention strategies, including control of carcinogenic bacteria, blockade of virulence factors, modulation of host responses, microenvironment remodeling, and integration with conventional therapies, providing a framework for precision CRC prevention and treatment.