Intratumoral microbiome: a key regulator and novel therapeutic target for chemoresistance in pancreatic cancer.

Pancreatic cancer is a highly lethal gastrointestinal malignancy with chemotherapy resistance as a major obstacle to improving prognosis. Emerging evidence indicates that the intratumoral microbiome is closely implicated in the development, progression, and therapeutic response of pancreatic cancer. The intratumoral microbiome of pancreatic cancer is mainly composed of Proteobacteria and Firmicutes, and its composition is significantly correlated with patient survival. Intratumoral microbes drive tumor progression by remodeling the immune microenvironment, inducing DNA damage, and activating oncogenic signaling pathways. Meanwhile, they exacerbate chemotherapy resistance via multiple mechanisms, including remodeling the extracellular matrix, establishing an immunosuppressive microenvironment, and metabolically inactivating chemotherapeutic agents. This review systematically summarizes the community composition of the intratumoral microbiome in pancreatic cancer, its regulatory effects, and underlying mechanisms on chemotherapy resistance, as well as the latest advances in targeted therapeutic strategies.