Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.

Science 2017 09;357(6356):1156-1160

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

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), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDD 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.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aah5043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727343PMC
September 2017
108 Reads
3 Citations
31.480 Impact Factor

Publication Analysis

Top Keywords

chemotherapeutic drug
8
intratumor bacteria
8
colon cancer
8
drug gemcitabine
8
induced intratumor
4
gemcitabine resistance
4
intratumor gammaproteobacteria
4
resistance induced
4
dependent bacterial
4
abrogated cotreatment
4
expression abrogated
4
cdd expression
4
bacterial cdd
4
gammaproteobacteria dependent
4
mouse model
4
long isoform
4
isoform bacterial
4
expression long
4
dependent expression
4
metabolism dependent
4

References

(Supplied by CrossRef)
Gemcitabine: Metabolism, mechanisms of action, and self-potentiation
Plunkett et al.
Semin. Oncol. 1995

Similar Publications