Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine
- PMID: 28912244
- PMCID: PMC5727343
- DOI: 10.1126/science.aah5043
Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine
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.
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Comment in
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Pancreatic cancer: Intra-tumour bacteria promote gemcitabine resistance in pancreatic adenocarcinoma.Nat Rev Gastroenterol Hepatol. 2017 Nov;14(11):632. doi: 10.1038/nrgastro.2017.142. Epub 2017 Oct 11. Nat Rev Gastroenterol Hepatol. 2017. PMID: 29018273 No abstract available.
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Cancer treatment: Bacterial snack attack deactivates a drug.Nature. 2017 Oct 18;550(7676):337-339. doi: 10.1038/550337a. Nature. 2017. PMID: 29052621 No abstract available.
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