The microbiome of pancreatic cancer: from molecular diagnostics to new therapeutic approaches to overcome chemoresistance caused by metabolic inactivation of gemcitabine

Abstract

<b>Introduction</b>: Pancreatic cancer is a complex disease, with an extremely poor response to chemotherapy. Emerging evidence indicates that the tumor microenvironment (TME) might play an important role in mediating chemoresistance. <b>Areas covered</b>: The evaluated study by Geller and collaborators describes several bacterial species within pancreatic tumor tissues and TME and investigated their roles in gemcitabine chemoresistance. Intratumor bacteria express the enzyme cytidine deaminase (CDD), whose long form (CDD_L) was shown to metabolize gemcitabine into its inactive metabolite. CDD_L is mostly expressed by <i>Gammaproteobacteria</i> and this was among the most common species in pancreatic cancer tissues. Interestingly, mouse models of colorectal cancer injected with bacterial CDD_L displayed a reduced response to gemcitabine, but this resistance was neutralized by the antibiotic ciprofloxacin. <b>Expert Commentary</b>: The increased knowledge on the microbiome in pancreatic tissues, as well as its role in chemoresistance, will provide innovative prognostic and therapeutic strategies.