Scientists have discovered that bacteria living inside tumors can produce a molecule that fights cancer and strengthens the effects of chemotherapy. This molecule, known as 2-methylisocitrate (2-MiCit), was found to make colorectal cancer cells more susceptible to chemotherapy by damaging their DNA and disrupting cellular metabolism. Its anti-cancer effects were confirmed using worms, flies, and human cancer cells.
An international team led by researchers at the MRC Laboratory of Medical Sciences (LMS), Imperial College London, and the University of Cologne revealed that tumor-associated microbes produce chemicals capable of controlling cancer progression and boosting chemotherapy efficacy. While many are familiar with bacteria in the gut or on the skin, tumors also host unique microbial communities, whose interactions with cancer cells are only beginning to be understood.
Published in Cell Systems on September 10, 2025, the study represents a significant breakthrough. Using large-scale screening in the microscopic worm C. elegans, the researchers identified that E. coli produces 2-MiCit, enhancing the chemotherapy drug 5-fluorouracil (5-FU). Computational modeling confirmed that tumor microbiomes from patients could similarly generate 2-MiCit. Experiments in human cancer cells and a fly model of colorectal cancer further demonstrated the molecule’s potent anti-cancer properties, including extended survival in flies.
Professor Filipe Cabreiro, head of the Host-Microbe Co-Metabolism group at LMS, explained: “One of these bacterial chemicals can act as a powerful partner for chemotherapy, disrupting cancer cell metabolism and increasing drug sensitivity.” The molecule works by inhibiting a key mitochondrial enzyme, triggering DNA damage and pathways that reduce cancer progression. Combined with 5-FU, it proved far more effective than either treatment alone.
Further collaboration with medicinal chemists led to a synthetic version of 2-MiCit, which showed enhanced potency against cancer cells. Dr. Daniel Martinez-Martinez, first author, noted, “A single microbial molecule can profoundly impact cancer, highlighting the complex biology of tumors.” These findings underscore the potential of tumor-associated microbes in developing new cancer therapies and advancing personalized medicine.
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