Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine
Name
nihms920919.pdf
Description
Accepted version
Size
1 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Geller, Leore T.
Barzily-Rokni, Michal
Danino, Tal
Jonas, Oliver H.
Shental, Noam
Nejman, Deborah
Gavert, Nancy
Zwang, Yaara
Cooper, Zachary A.
Shee, Kevin
Date Issued
September 2017
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Geller, Leore T. et al. "Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine." 357, 6356 (September 2017): 1156-1160 © 2017 The Authors
Version
Author's final manuscript
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 (CDD L ), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDD L 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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/science.aah5043
