Abstract IA12: Fusobacterium persistence and antibiotic response in colorectal cancer

Abstract

Abstract In colorectal cancer (CRC), malignant cells are surrounded by a complex microenvironment encompassing a range of nontransformed cells, but also a diverse collection of microorganisms. A growing body of evidence demonstrates the role of particular microorganisms in modulating inflammatory environments and promoting tumor growth and metastasis. Genomic analyses have consistently revealed an enrichment of the invasive bacterium Fusobacterium nucleatum in human colorectal tumors relative to noncancerous colorectal tissues. Exogenous F. nucleatum infection in animal and cellular models has also supported its cancer-promoting role. We demonstrate via microbiome analysis and microbial culture that Fusobacterium species and their co-occurring microbiota, including Bacteroides, Prevotella, and Selenomonas species, persist in liver metastasis of Fusobacterium-positive CRC. Many of the liver metastasis share the same dominant microbiome as the paired primary CRC tumors. Additionally, we have cultured Fusobacterium species from paired primary and metastatic tumors, and whole-genome sequencing analysis revealed that the same strains of Fusobacterium are present in the primary tumors and distant site metastasis, despite the tissue being resected months or even years apart. In situ hybridization analyses show that Fusobacterium is invasive in the primary tumors and distal metastasis and is associated with malignant cells. We demonstrate via microbiome analysis and microbial culture that Fusobacterium and its co-occurring microbiota also persist and remain viable in patient-derived xenografts of CRC for multiple generations in vivo. Antibiotic treatment of mice harboring these patient colon cancer xenografts led to a significant reduction in tumor Fusobacterium load, cancer cell proliferation, and overall tumor growth, suggesting that microbiome modulation could change the course of this disease. Ultimately, if a bacterial agent can directly or indirectly contribute to cancer initiation or progression, then these organisms are viable targets for cancer prevention and treatment. Citation Format: Susan Bullman. Fusobacterium persistence and antibiotic response in colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA12.