Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357:1156–1160.
NOTES
Geller, Leore TBarzily-Rokni, MichalDanino, TalJonas, Oliver HShental, NoamNejman, DeborahGavert, NancyZwang, YaaraCooper, Zachary AShee, KevinThaiss, Christoph AReuben, AlexandreLivny, JonathanAvraham, RoiFrederick, Dennie TLigorio, MatteoChatman, KellyJohnston, Stephen EMosher, Carrie MBrandis, AlexanderFuks, GaroldGurbatri, CandiceGopalakrishnan, VancheswaranKim, MichaelHurd, Mark WKatz, MatthewFleming, JasonMaitra, AnirbanSmith, David ASkalak, MattBu, JeffreyMichaud, MoniaTrauger, Sunia ABarshack, IrisGolan, TaliaSandbank, JudithFlaherty, Keith TMandinova, AnnaGarrett, Wendy SThayer, Sarah PFerrone, Cristina RHuttenhower, CurtisBhatia, Sangeeta NGevers, DirkWargo, Jennifer AGolub, Todd RStraussman, RavidengP30 DK043351/DK/NIDDK NIH HHS/R01 CA154426/CA/NCI NIH HHS/R01 CA169086/CA/NCI NIH HHS/U54 CA112962/CA/NCI NIH HHS/K08 CA160692/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tScience. 2017 Sep 15;357(6356):1156-1160. doi: 10.1126/science.aah5043.
Abstract
Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.
Last updated on 02/17/2021