Gut microbiota–cancer crosstalk: emerging molecular targets for personalized cancer treatment- a comprehensive review

Abstract

Cancer remains a major global health challenge, and growing evidence indicates that the gut microbiota plays an important role in cancer initiation, progression, metastasis, and response to treatment through complex interactions with host signaling, metabolism, and immunity. This comprehensive narrative review discusses the molecular mechanisms underlying gut microbiota–cancer crosstalk, with particular emphasis on dysbiosis, microbial metabolites, immune modulation, and microbiota-regulated oncogenic pathways, including TLR/NF-κB, Wnt/β-catenin, JAK/STAT, PI3K/Akt/mTOR, and Hippo-YAP signaling. The review also examines emerging molecular targets, including microbial extracellular vesicles, bacterial small RNAs, ferroptosis-related mechanisms, and microbiota–mitochondria interactions. In addition, current microbiota-targeted therapeutic strategies, such as fecal microbiota transplantation, engineered bacterial therapeutics, CRISPR-based microbiome engineering, and microbiome-informed approaches to precision oncology are discussed. Relevant peer-reviewed literature published primarily within the recent 5-year period was considered from major scientific databases and publisher platforms, including PubMed, Scopus, Web of Science, Springer, Elsevier, and MDPI. Overall, the available evidence suggests that gut microbiota represents an important component of the tumor ecosystem and may provide promising biomarkers and therapeutic targets. Integration of microbiome research with multi-omics and artificial intelligence may further support the development of personalized cancer treatment.