Journal
SCIENCE
Volume 358, Issue 6369, Pages 1443-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aal5240
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Funding
- NIH [R35 CA197568, R35 CA197735, K07 CA148894, R01 CA118553, R01 CA169141]
- Dana-Farber/Harvard Cancer Center GI SPORE P50 grant [CA 127003]
- American Cancer Society Research Professorship
- Hale Family Center for Pancreatic Cancer
- Project P Fund for Colorectal Cancer Research
- Stand-up-to Cancer (Colorectal Cancer Dream Team) the Chambers Family Fund for Colorectal Cancer Research
- Team Perry Fund
- Clark Family Fund for GI Cancer Research
- Prevent Cancer Foundation Figdor Family Fellowship
- Cellex Private Foundation
- Banco Bilbao Vizcaya Argentaria Foundation
- Eli Lilly Genentech
- Merck
- Sanofi
- Five Prime Therapeutics
- Merrimack Pharmaceuticals
- Bayer
- Agios Pharmaceuticals
- Lair Oncology
- KEW Group
- National Center for Biotechnology Information (NCBI) [PRINA362951]
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Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome-including Bacteroides, Selenomonas, and Prevotella species-is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.
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