Microbiome Drug Interactions in Cancer Pharmacology: Mechanisms and Therapeutic Opportunities

INTRODUCTION: Interindividual variability in cancer therapy response cannot be fully explained by host genetics or tumor characteristics alone. Emerging evidence indicates that the gut microbiome is a critical modulator of anticancer drug metabolism, immune responses, and therapeutic outcomes, positioning it as an important determinant in cancer pharmacology. METHODS: This narrative review employed a structured literature search of PubMed, Scopus, and Web of Science (2005-2025) to synthesise preclinical and clinical evidence on microbiome-drug interactions, focusing on pharmacokinetics, immune modulation, toxicity, and resistance across chemotherapy, immunotherapy, and targeted therapies. RESULTS AND DISCUSSION: The gut microbiome influences anticancer therapy through enzymatic biotransformation, immune regulation, metabolite signalling, and maintenance of intestinal barrier integrity. Clinically, favourable microbiome profiles have been associated with improved immunotherapy outcomes, with reported hazard ratios for survival ranging from ~0.5 to 0.7, while prior antibiotic exposure is linked to a 20-40% reduction in response rates. Microbial enzymes such as β- glucuronidase contribute to irinotecan-induced toxicity, affecting up to 20-40% of patients. Specific taxa, including Akkermansia muciniphila and Bifidobacterium spp., are associated with enhanced therapeutic response. Microbiome-targeted interventions, including faecal microbiota transplantation, have demonstrated response restoration in approximately 30-40% of refractory cases in early clinical studies. However, heterogeneity in microbial composition, lack of standardisation, and safety concerns limit clinical translation. CONCLUSION: The gut microbiome represents an adaptable determinant of cancer pharmacology. Integrating microbiome-informed strategies offers a promising pathway toward precision oncology, although robust clinical validation remains essential for routine implementation.