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

Arthur T. F. Choy, Ilaria Carnevale, Stefano Coppola, Laura L. Meijer, Geert Kazemier, Egija Zaura, Dongmei Deng, Elisa Giovannetti

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: 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. Areas covered: 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 (CDDL) was shown to metabolize gemcitabine into its inactive metabolite. CDDL is mostly expressed by Gammaproteobacteria and this was among the most common species in pancreatic cancer tissues. Interestingly, mouse models of colorectal cancer injected with bacterial CDDL displayed a reduced response to gemcitabine, but this resistance was neutralized by the antibiotic ciprofloxacin. Expert Commentary: The increased knowledge on the microbiome in pancreatic tissues, as well as its role in chemoresistance, will provide innovative prognostic and therapeutic strategies.
Original languageEnglish
Pages (from-to)1005-1009
JournalExpert review of molecular diagnostics
Volume18
Issue number12
Early online date5 Nov 2018
DOIs
Publication statusPublished - 2018

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