Bacteria in tumors produce molecule to boost cancer chemotherapy
Scientists have identified a molecule produced by bacteria inside tumors that enhances the effectiveness of chemotherapy against colorectal cancer. The compound, 2-methylisocitrate, damages cancer cell DNA and disrupts their metabolism. This discovery could lead to new treatments that make existing drugs more potent.
An international team led by researchers at the MRC Laboratory of Medical Sciences in London, Imperial College London, and the University of Cologne has uncovered how tumor-associated bacteria influence cancer progression. Published online in Cell Systems on September 10, 2025, the study reveals that these microbes produce 2-methylisocitrate (2-MiCit), a metabolite that synergizes with the chemotherapy drug 5-fluorouracil (5-FU).
The researchers screened over 1,100 conditions using the worm C. elegans and found that E. coli bacteria generate 2-MiCit, which improves 5-FU's impact. Computer modeling confirmed that patient tumor microbiomes also produce this molecule. Further validation in human colorectal cancer cells and a fly model showed 2-MiCit's anti-cancer effects, including extended survival in flies.
Professor Filipe Cabreiro, head of the Host-Microbe Co-Metabolism group at the LMS, explained: "We've known that bacteria are associated with tumors, and now we're starting to understand the chemical conversation they're having with cancer cells. We found that one of these bacterial chemicals can act as a powerful partner for chemotherapy, disrupting the metabolism of cancer cells and making them more vulnerable to the drug."
The molecule inhibits a key mitochondrial enzyme, causing DNA damage and activating pathways that slow cancer growth. Combined with 5-FU, it kills cancer cells more effectively than either alone. Dr. Daniel Martinez-Martinez, the study's first author, noted: "Microbes are an essential part of us. That a single molecule can exert such a profound impact on cancer progression is truly remarkable, and another piece of evidence on how complex biology can be when considering it from a holistic point of view."
Collaborators modified 2-MiCit into a more potent synthetic version, highlighting potential for microbe-inspired drugs. Funded by the Leverhulme Trust, Wellcome Trust/Royal Society, DFG, and Medical Research Council, the work underscores the role of the tumor microbiome in personalized medicine.