Microbiota in cancer: current understandings and future perspectives

Abstract The intricate relationship between the microbiota and cancer has recently emerged as a pivotal area of research, highlighting their critical roles in carcinogenesis, progression, and prognosis. With the increasing recognition of the therapeutic potential of the microbiota in cancer, there is an urgent need to understand the diverse impacts of different microbiota on tumors and explore innovative strategies to harness their benefits. For the first time, this review traces the historical evolution of microbiota–cancer studies, from early observations of microbial presence in cancers to landmark discoveries linking specific microorganisms to carcinogenesis. Furthermore, this study delves into the molecular mechanisms underlying microbiota-mediated cancer progression to elucidate the modulatory roles of oncogenic pathways, immune responses, and tumor metabolism. We also discuss the dual roles of the microbiota in promoting and inhibiting cancer, highlighting its potential as both a facilitator of tumor growth and a target for therapeutic intervention. In addition, this review highlights the mechanism by which the microbiota mediates the response to anticancer immunotherapy, chemotherapy, and radiotherapy. Simultaneously, emerging anticancer strategies targeting microbiota (e.g., probiotics, antibiotics, and fecal microbiota transplantation) have been explored alongside U.S. Food and Drug Administration-approved drugs and ongoing clinical trials. Finally, this review outlines future directions in this field, emphasizing the need for personalized approaches to harness the anticancer potential of the microbiota. The interpretations in this review are expected to establish a stereoscopic, comprehensive framework for advancing research and clinical applications in microbiota-targeted oncology.