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

Leore T. Geller | Zendy; Michal Barzily-Rokni | Zendy; Tal Danino | Zendy; Oliver Jonas | Zendy; Noam Shental | Zendy; Deborah Nejman | Zendy; Nancy Gavert | Zendy; Yaara Zwang | Zendy; Zachary A. Cooper | Zendy; Kevin Shee | Zendy; Christoph A. Thaiss | Zendy; Alexandre Reuben | Zendy; Jonathan Livny | Zendy; Roi Avraham | Zendy; Dennie T. Frederick | Zendy; Matteo Ligorio | Zendy; Kelly Chatman | Zendy; Stephen Johnston | Zendy; Carrie M. Mosher | Zendy; Alexander Brandis | Zendy; Garold Fuks | Zendy; Candice R. Gurbatri | Zendy; Vancheswaran Gopalakrishnan | Zendy; Michael P. Kim | Zendy; Mark W. Hurd | Zendy; Matthew H. G. Katz | Zendy; Jason B. Fleming | Zendy; Anirban Maitra | Zendy; David A. Smith | Zendy; Matt Skalak | Zendy; Jeffrey Bu | Zendy; Monia Michaud | Zendy; Sunia A. Trauger | Zendy; Iris Barshack | Zendy; Talia Golan | Zendy; Judith Sandbank | Zendy; Keith T. Flaherty | Zendy; Anna Mandinova | Zendy; Wendy S. Garrett | Zendy; Sarah P. Thayer | Zendy; Cristina R. Ferrone | Zendy; Curtis Huttenhower | Zendy; Sangeeta N. Bhatia | Zendy; Dirk Gevers | Zendy; Jennifer A. Wargo | Zendy; Todd R. Golub | Zendy; Ravid Straussman | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

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

Author(s) -

Leore T. Geller,

Michal Barzily-Rokni,

Tal Danino,

Oliver Jonas,

Noam Shental,

Deborah Nejman,

Nancy Gavert,

Yaara Zwang,

Zachary A. Cooper,

Kevin Shee,

Christoph A. Thaiss,

Alexandre Reuben,

Jonathan Livny,

Roi Avraham,

Dennie T. Frederick,

Matteo Ligorio,

Kelly Chatman,

Stephen Johnston,

Carrie M. Mosher,

Alexander Brandis,

Garold Fuks,

Candice R. Gurbatri,

Vancheswaran Gopalakrishnan,

Michael P. Kim,

Mark W. Hurd,

Matthew H. G. Katz,

Jason B. Fleming,

Anirban Maitra,

David A. Smith,

Matt Skalak,

Jeffrey Bu,

Monia Michaud,

Sunia A. Trauger,

Iris Barshack,

Talia Golan,

Judith Sandbank,

Keith T. Flaherty,

Anna Mandinova,

Wendy S. Garrett,

Sarah P. Thayer,

Cristina R. Ferrone,

Curtis Huttenhower,

Sangeeta N. Bhatia,

Dirk Gevers,

Jennifer A. Wargo,

Todd R. Golub,

Ravid Straussman

Publication year - 2017

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aah5043

Subject(s) - gemcitabine , drug resistance , drug , bacteria , chemotherapeutic drugs , cancer research , biology , pharmacology , microbiology and biotechnology , chemotherapy , genetics

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research