| Literature DB >> 28912244 |
Leore T Geller1, Michal Barzily-Rokni2, Tal Danino3, Oliver H Jonas4,5, Noam Shental6, Deborah Nejman1, Nancy Gavert1, Yaara Zwang1, Zachary A Cooper7,8, Kevin Shee2, Christoph A Thaiss9, Alexandre Reuben8, Jonathan Livny2, Roi Avraham10, Dennie T Frederick11, Matteo Ligorio12, Kelly Chatman13, Stephen E Johnston2, Carrie M Mosher2, Alexander Brandis14, Garold Fuks15, Candice Gurbatri16, Vancheswaran Gopalakrishnan8, Michael Kim8, Mark W Hurd17, Matthew Katz8, Jason Fleming8, Anirban Maitra18, David A Smith2, Matt Skalak3, Jeffrey Bu3, Monia Michaud19, Sunia A Trauger13, Iris Barshack20,21, Talia Golan21,22, Judith Sandbank21, Keith T Flaherty12, Anna Mandinova2,23, Wendy S Garrett2,19,24, Sarah P Thayer25, Cristina R Ferrone26, Curtis Huttenhower2,27, Sangeeta N Bhatia2,28,29,30,31,32,33, Dirk Gevers2, Jennifer A Wargo7,8, Todd R Golub34,35,36, Ravid Straussman37.
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.Entities:
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Year: 2017 PMID： 28912244 PMCID： PMC5727343 DOI： 10.1126/science.aah5043
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728