TY - JOUR
T1 - The microbiome of pancreatic cancer
T2 - from molecular diagnostics to new therapeutic approaches to overcome chemoresistance caused by metabolic inactivation of gemcitabine
AU - Choy, Arthur T. F.
AU - Carnevale, Ilaria
AU - Coppola, Stefano
AU - Meijer, Laura L.
AU - Kazemier, Geert
AU - Zaura, Egija
AU - Deng, Dongmei
AU - Giovannetti, Elisa
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85057320616&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30392417
U2 - 10.1080/14737159.2018.1544495
DO - 10.1080/14737159.2018.1544495
M3 - Article
C2 - 30392417
VL - 18
SP - 1005
EP - 1009
JO - Expert review of molecular diagnostics
JF - Expert review of molecular diagnostics
SN - 1473-7159
IS - 12
ER -