Pancreatic Cancer Meets Human Microbiota: Close Encounters of the Third Kind

Simple Summary The microorganisms colonizing the epithelial surfaces of the human body, called microbiota, have been shown to influence the initiation, progression and response to therapy of many solid tumors, including pancreatic ductal adenocarcinoma, the most prominent form of pancreatic cancer. Here, we summarize the current knowledge about the influence of oral, gut and intratumoral microbiota on pancreatic ductal adenocarcinoma development and chemoresistance. Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer with a dismal prognosis. The five-year survival rate has not changed significantly in over 40 years. Current first-line treatments only offer a modest increase in overall survival in unselected populations, and there is an urgent need to personalize treatment in this aggressive disease and develop new therapeutic strategies. Evolving evidence suggests that the human microbiome impacts cancerogenesis and cancer resistance to therapy. The mechanism of action and interaction of microbiome and PDAC is still under investigation. Direct and indirect effects have been proposed, and the use of several microbiome signatures as predictive and prognostic biomarkers for pancreatic cancer are opening new therapeutic horizons. In this review, we provide an overview for the clinicians of studies describing the influence and associations of oral, gastrointestinal and intratumoral microbiota on PDAC development, progression and resistance to therapy and the potential use of microbiota as a diagnostic, prognostic and predictive biomarker for PDAC.