Targeting Microbiome-Derived Exosomes to Overcome Cancer Therapy Resistance: Mechanisms, Implications, and Opportunities.

Despite recent advances in both preclinical and clinical cancer therapies, the growing problem of treatment resistance remains one of the most critical challenges in oncology. To overcome the drawbacks of current oncologic treatments, there is a pressing need for new approaches and potential therapeutic strategies. The interaction between the host microbiome and cancer has recently attracted significant research. Among the various routes of microbiome-cancer interaction, microbiome-derived exosomes also offer an intriguing avenue. Exosomes, which are small extracellular vesicles, originate from several distinct types of cells, including microbiome-associated cells. These vesicles participate in intra- and intercellular communication as well as alteration of the tumour microenvironment. Emphasising their possible functions as treatment response modifiers and mediators, this review seeks to explain an intricate link between cancer therapy resistance and exosomes produced from the microbiome. Preclinical studies reveal that microbiome-derived exosomes operate through horizontal transfer of resistance-conferring enzymes and TLR4/MYD88-dependent signalling, demonstrating 2-5 fold upregulation of resistance-associated miRNAs in drug-resistant models. Clinical evidence shows