Fusobacterium in colorectal cancer
Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide, and a substantial subset is driven and worsened by Fusobacterium nucleatum, a Gram-negative oral anaerobe that selectively colonizes tumor tissue, promotes proliferation and epithelial-mesenchymal transition, recruits immunosuppressive myeloid cells, and confers resistance to chemotherapy (via autophagy induction) and to immune checkpoint blockade. Broad-spectrum antibiotics can lower Fn burden but cause collateral gut dysbiosis and select for resistance, making a precision antibacterial highly desirable. Bacteriophages are a natural fit: they are exquisitely host-specific, so an anti-Fn phage can deplete the tumor-promoting bacterium while sparing beneficial commensals, and they self-amplify at the site of infection. This specificity reframes Fn-positive CRC as a potentially "treatable infection" layered on top of standard oncology care.
How phages act here
Mechanism
Phages targeting F. nucleatum bind strain-specific surface receptors and either lyse the bacterium directly (e.g., the lytic phage ØTCUFN3) or serve as molecular homing devices in engineered "biotic-abiotic" hybrids. In the landmark Wuhan University work, an Fn-binding phage was azide-modified and covalently conjugated to irinotecan-loaded dextran nanoparticles, so the phage guides chemotherapy precisely to Fn-colonized tumor tissue, depleting the bacterium and overcoming Fn-driven chemoresistance. A related M13 phage screened by phage display was electrostatically coated with silver nanoparticles (M13@Ag): the M13 capsid delivers the bactericidal silver to Fn in the gut, scavenging it and reducing myeloid-derived suppressor cell (MDSC) accumulation, while the phage itself activates antigen-presenting cells—remodeling the immunosuppressive tumor microenvironment. Phage-antibiotic and phage-immunotherapy synergy is central: M13@Ag combined with anti-PD-1 or FOLFIRI markedly prolonged survival in orthotopic CRC models, illustrating that anti-Fn phages act less as standalone cures than as sensitizers that restore the efficacy of chemotherapy and checkpoint inhibitors. Because Fn forms antibiotic-tolerant biofilms on tumors, phage/nanoparticle delivery is also being explored to penetrate where antibiotics fail.
Where it stands
Current evidence
As of 2026 the evidence is entirely preclinical—robust proof-of-concept in vitro and in mouse (and some piglet safety) models, but no registered human clinical trial yet evaluates anti-Fn phage therapy for CRC. Key milestones: Zheng et al. (Nature Biomedical Engineering, 2019) showed phage-guided irinotecan nanoparticles augmented first-line chemotherapy in Apc-mutant and orthotopic CRC mice, with negligible toxicity in piglets; Dong et al. (Science Advances, 2020) showed the M13@Ag hybrid cleared gut Fn, reduced MDSCs, and synergized with anti-PD-1 and FOLFIRI to extend survival. Most recently, Lam et al. (Antibiotics, 2025) isolated a novel naturally lytic Fn phage, ØTCUFN3, that inhibited Fn-induced CRC cell proliferation and EMT marker expression and shrank Fn-induced mouse xenografts—an advance toward a "drug-like" lytic phage rather than a nanoparticle vehicle. Gut-phageome profiling (Shen et al., 2021) further identified Fn-phage signatures as candidate CRC biomarkers. The field still lacks GMP phage banks, validated delivery to tumor-resident Fn, and human safety/efficacy data.
Evidence confidence: medium
The data
Key studies & trials
- Zheng DW, Dong X, Pan P, Chen KW, Fan JX, Cheng SX, Zhang XZ. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy. Nature Biomedical Engineering. 2019;3(9):717-728. ↗
- Dong X, Pan P, Zheng DW, Bao P, Zeng X, Zhang XZ. Bioinorganic hybrid bacteriophage for modulation of intestinal microbiota to remodel tumor-immune microenvironment against colorectal cancer. Science Advances. 2020;6(20):eaba1590. ↗
- Lam HYP, Lai MJ, Wang PC, Wu WJ, Chen LK, Fan HW, Tseng CC, Peng SY, Chang KC. A Novel Bacteriophage with the Potential to Inhibit Fusobacterium nucleatum-Induced Proliferation of Colorectal Cancer Cells. Antibiotics (Basel). 2025;14(1):45. ↗
- Shen S, Huo D, Ma C, Jiang S, Zhang J. Expanding the Colorectal Cancer Biomarkers Based on the Human Gut Phageome. Microbiology Spectrum. 2021;9(3):e0009021. ↗
Who is working on it
Programs & centers
The possibility
Imagine a colonoscopy that not only stages a tumor but types its resident Fusobacterium, followed by an oral, refrigerator-stable cocktail of lytic phages that hunts the bacterium through the tumor's biofilm while leaving the rest of the microbiome intact—converting a checkpoint-inhibitor-resistant tumor into a responsive one. Engineered and CRISPR-armed phages could go further, delivering payloads that simultaneously kill Fn and flip the tumor's immune environment from cold to hot, turning a microbial accomplice of cancer into a precision therapeutic target. Paired with chemotherapy and immunotherapy as a "microbiome adjuvant," anti-Fn phages could become one of the first examples of treating a cancer by treating its bacteria.