The tumor microbiome in cancer progression: mechanisms and therapeutic potential

The tumor microbiome (TM) comprises diverse microbial communities, such as bacteria, fungi, and viruses. Recent advancements in microbial sequencing technologies have improved our understanding of the distribution and functional roles of microbes in solid tumors. The TM is formed through several mechanisms, such as direct invasion of mucosal barriers, diffusion from adjacent normal tissues, metastasis of tumor cells, and dissemination via blood and lymphatic circulation. Microbes play a critical role in the tumor microenvironment (TME), and the TM has a heterogeneous composition in different types of cancer. This heterogeneity affects tumor development, progression, and response to treatment. The TM modulates tumor cell physiology and immune responses via several signaling pathways, such as WNT/β-catenin, NF-κB, toll-like receptors (TLRs), ERK, and stimulator of interferon genes (STING). Extensive studies have characterized the role of TM in tumor progression, revealing the importance of genetic abnormalities, epigenetic changes, metabolic regulation, invasion and metastasis, and chronic inflammatory responses. The role of TM in cancer treatment, especially in immunotherapy, has received increasing attention, demonstrating significant regulatory potential. This review provides an in-depth overview of the development of TM detection technologies, explores its potential origins and heterogeneity, and elucidates the mechanisms by which TM contributes to tumorigenesis or tumor suppression. Furthermore, this review explored how TM can be used in cancer treatment, offering a comprehensive perspective on targeted and personalized approaches.