Molecular studies on the impact of microbiome on anticancer drug resistance.

Abstract

Cancer remains a leading global health challenge, with drug resistance posing a critical barrier to the durable efficacy of anticancer therapies, including chemotherapy, immunotherapy, and targeted treatments. Growing evidence highlights the gut microbiome as a key modulator in this resistance process. The gut microbiome-a dynamic and diverse microbial ecosystem-can influence drug efficacy through multiple mechanisms, including the biotransformation of chemotherapeutics, modulation of immune responses, alteration of host drug-metabolizing enzymes, and reshaping of the tumor microenvironment. Notably, specific bacterial taxa can enzymatically inactivate chemotherapeutic drugs, while microbial metabolites and signaling pathways further promote resistance by rewiring cellular survival and immune-regulatory programs. In this review, we synthesize recent molecular insights into microbiome-driven anticancer drug resistance and discuss emerging microbiome-targeted strategies, such as dietary intervention, probiotics and prebiotics, fecal microbiota transplantation, and advanced drug delivery systems. A deeper understanding of host-microbiome-drug interactions may provide new opportunities to overcome therapeutic resistance and advance precision oncology.